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Tottenham captain Cristian Romero will miss the remainder of the season with a knee injury.
The defender was substituted in tears during Sunday's 1-0 defeat at Sunderland following a collision with Spurs goalkeeper Antonin Kinsky while defending the ball from Sunderland striker Brian Brobbey.
Reports claiming the Argentina international will return in time for the World Cup are believed not to be completely accurate, but Romero's season at club level is over.
Are Spurs destined for relegation? | Carra: Spurs look like they're going down
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Romero's injury is another monumental blow for relegation-threatened Spurs, who are in the bottom three and two points from safety with only six league games remaining.
It is another injury issue for new Spurs boss Roberto De Zerbi, who told reporters on Friday he had expected to rely on Mohammed Kudus only for the forward to suffer a fresh quad injury.
Now he will have to do without Romero for the run-in, whom he had labelled a "crucial player" after the defeat at the Stadium of Light.
When asked about Romero's injury on Sunday, he said: "I hope for us it's not too important a problem because he's a crucial player for us.
"He's a good guy, good player, top player, big personality and we need him to finish this season and to achieve our goal."
Kevin Danso is line to replace Romero for the remainder of the season after the Austria international came on for him in the defeat at Sunderland.
Romero is now facing a race to be fit in time for this summer's World Cup with Argentina aiming to defend the title in USA, Canada and Mexico.
Argentina's opening game of the tournament is on June 17.
Should Brobbey have been punished for push which led to Romero injury?
Romero's season-ending injury came as a result of a push by Brobbey, who was already on a yellow card, leading to questions over whether the striker should have been sent off.
Speaking on Sky Sports News' Ref Watch, ex-Premier League referee Dermot Gallagher said: "We have to be careful we don't get seduced by the outcome - the injury.
"If the goalkeeper's not there, a little nudge, are you going to send him off for a second yellow card? The answer is most certainly no.
"The goalkeeper comes out and a collision occurs. That changes everyone's perspective, but it wasn't a serious foul."
Ex-Cardiff striker Jay Bothroyd added: "Romero is not in control of the ball and is trying to block Brobbey from getting it. At some point, Brobbey can't see the ball anymore because he's so close to Romero.
"It's almost like he's pushed him to one side to see it. That's the kind of incident that comes because defenders are trying to shield the ball."
Are Tottenham destined for relegation?
Many of Tottenham's biggest issues were self-diagnosed by Roberto De Zerbi during his first game in charge. Spurs had fallen into the bottom three before travelling to Sunderland, and their performance in defeat did nothing to strengthen the belief that they can climb out of it.
Appointing De Zerbi as one of the highest-paid head coaches in the division at this juncture of an already calamitous campaign was a high-stakes gamble. Some might argue that keeping Igor Tudor on would have been riskier still.
But whoever the boss - De Zerbi is Spurs' fourth of the last 12 months - the same problems seem to persist.
Sky Sports' Laura Hunter analyses De Zerbi's first game in charge.
Carra: Spurs look like they're going down
Sky Sports' Jamie Carragher:
"I can't believe it. Tottenham look like they're going to go down," said Carragher. "The other [relegation-threatened] teams have something going for them.
"You look at fixtures, you think that's a good game for Tottenham. But they're awful. Tottenham's a good game for them.
"Wolves are bottom of the league. Do you think Tottenham will go there, and win? No chance."
Tottenham's remaining games
Saturday: Brighton (H) - Premier League, kick-off 5.30pm, live on Sky Sports
April 25: Wolves (A) - Premier League, kick-off 3pm
May 2: Aston Villa (A) - Premier League, kick-off 12.30pm
May 11: Leeds (H) - Premier League, kick-off 8pm, live on Sky Sports
May 17: Chelsea (A) - Premier League
Many of Tottenham's biggest issues were self-diagnosed by Roberto De Zerbi during his first game in charge. Spurs had fallen into the bottom three before travelling to Sunderland and their performance in defeat did nothing to strengthen belief they can climb out of it.
Appointing De Zerbi at this juncture of an already calamitous campaign was a high-stakes gamble. Some might argue that keeping Igor Tudor on would have been riskier still. But whoever the head coach - De Zerbi is Spurs' fourth of the last 12 months - the same problems seem to persist.
Tottenham do not have a style to speak of. Perhaps that was part of the enigmatic Italian's appeal. De Zerbi clearly offers philosophy, a distinctive way of playing, and as evidenced by his time at Brighton, a high ceiling of performance level.
The complication is that this Spurs side in its current configuration is not capable of delivering against De Zerbi's plans. That much was evident at Sunderland. Nordi Mukiele's heavily-deflected effort was the nail in the coffin of a tepid offering and now the narrative has descended into analysis of increasing relegation probabilities.
Carra: Spurs look like they are going down
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What felt like an impossibly shocking consequence of severe underperformance, that had the power to goad but lacked genuine substance, now feels very probable indeed. One point from a possible 24 is desperate.
Spurs' 14-match winless Premier League run is their worst since 1935. They are increasingly compelling contenders for the drop. Perhaps, as Jamie Carragher hypothesised on Super Sunday, a more convincing case than those around them given recent form and confidence levels.
De Zerbi explained in his first press conference that he had had little time to implement his tactical ideas to face Sunderland, prioritising "character, the right spirit and the right courage to play". Barring a bright opening 10 minutes, Spurs were devoid of all three.
Something can at least be made of the theory behind De Zerbi's set-up, if not the implementation.
He packed central areas with legs and energy as Conor Gallagher and Lucas Bergvall played ahead of Archie Gray - with sound intention - but in trying to dominate the ball they contrived to lose the battle.
Granit Xhaka, Noah Sadiki and Habib Diarra proved a far more accomplished trio. Xhaka controlled the tempo; his touch count (85) was the highest of any player on the park and he generated a game-high 16 passes into the final third.
Sunderland goalkeeper Robin Roefs actually played more final-third passes (nine) than all three of Tottenham's midfielders.
Out of possession the hosts were far superior, too, winning more tackles, successfully contesting more duels and making a greater number of interceptions. Spurs were able to land seven shots on target but only one of those was deemed a big chance and that was fluffed by Dominic Solanke.
Full-back Pedro Porro was the best hope of open-play threat. That does not reflect well on Spurs' attacking contingent.
De Zerbi is an ideas man but he is chronically short of fit creators. One must therefore question the decision to leave Xavi Simons in reserve on Sunday; the Dutchman was only introduced with six minutes remaining. Is that enough time to impact a game Spurs had trailed since the hour mark?
This six-game gauntlet will be decided by decisions such as that. The situational severity means they must be right.
Spurs' new custodian will have had two weeks to get to grips with his playing squad by the time former employers Brighton visit the Tottenham Hotspur Stadium on Saturday evening. He will not have lavish means by which to beat the side he guided to sixth place in 2022/23, but there are tangible improvements to be made.
Spurs have to start on the front foot to face this crisis head on. The north Londoners are winless in each of their last 32 Premier League games after going behind - only eight of those were draws. They have only spent 18.3 per cent of games in winning positions all season.
It has been nearly four months since they last tasted victory in the league, long enough to have forgotten exactly what that feels like or how it is achieved, but whatever the variables this weekend Tottenham must find a way to win.
They must draw from the well of relegation fear with greater effectiveness, especially in moments of misfortune. Games simply escape Tottenham too easily after they suffer a setback and it was no surprise to see Mukiele's effort that cannoned cruelly off the leg of Micky van de Ven be enough to settle Sunday's contest.
That is how fragile Spurs are.
No time for despondence, though. Survival scraps do not entertain sentiment. Theoretically this is a team of good players, now it is up to De Zerbi to get them performing with the strength of character to prove it.
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Roberto De Zerbi's first game in charge of relegation-threatened Tottenham ended in a sombre 1-0 defeat at Sunderland.
The enigmatic Italian was parachuted into the Spurs hot seat with seven games to go, needing to rescue the Londoners from suffering a humiliating fate - a very different assignment to the last time he managed in the Premier League at Brighton.
The Seagulls, incidentally, will be the visitors next week when their former boss takes charge of his first home game at the Tottenham Hotspur Stadium, and he will do so from a position in the drop zone.
Tottenham remain winless in their last 14 Premier League outings, their second-longest run without a league victory in club history, and are now two points from safety after falling foul of a Nordi Mukiele deflected strike in the second half at the Stadium of Light.
Spurs showed promise in fleeting moments, De Zerbi's imprint visible in their endeavour, but Robin Roefs was only threatened once by Dominic Solanke. The striker fluffed his effort and with it Spurs' chance of a foothold in a game they failed to properly impact.
As it happened | Teams | Stats
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Before the finish Destiny Udogie turned Chemsdine Talbi's attempt off the line, while captain Cristian Romero was forced off in tears with an undisclosed injury. His emotional state mirrored that of Spurs' general circumstance and now the unthinkable is a very real prospect indeed.
Sunderland, meanwhile, rise into the top half of the table as their remarkable return to the Premier League continues. The fortunes of the two sides could not have been more contrasting on yet another forgettable afternoon for the plight of Tottenham Hotspur.
Carragher: Other relegation rivals have better chance than Spurs
Sky Sports' Jamie Carragher:
"Normally a new manager comes in and you say it's his first game, that has to go out the window. It had to go out the window for Igor Tudor and it's the same for Roberto de Zerbi because of where they find themselves.
"I can't believe it. Tottenham look like they're going to go down.
"The other teams have something going for them. One point in 24?
"You look at fixtures, you think that's a good game for Tottenham, but they're awful. Tottenham's a good game for every other club.
"Wolves are bottom of the league. Do you think Tottenham will go there and win? No chance."
Wake up: Spurs' slide is real
Analysis by Sky Sports' Laura Hunter:
What began as a day of promise for the inception of the Roberto De Zerbi era ended in a crushing reality: Is this Tottenham side really good enough to stay in the Premier League?
For the majority of this season the narrative has been framed differently. Those of us that comment routinely were posing the question: Are Tottenham really bad enough to go down? Most would answer no. But that stance is swiftly changing.
Spurs are compelling relegation contenders. Perhaps, as Jamie Carragher hypothesised, a more convincing case than those around them given form and confidence levels.
Only Derby, Sunderland and Swindon Town have endured longer winless runs to start a calendar year in the top-flight than Spurs' current streak and all three were relegated in their respective campaigns. De Zerbi needs a miracle to prevent the same fate.
All the warning signs are there. And now what felt like an impossibly shocking eventuality, that had little genuine substance, feels very probable indeed.
De Zerbi: We didn't deserve to lose
Tottenham boss Roberto De Zerbi:
"I think we played a good game but not enough to win. We didn't deserve to lose the game but we have to accept and have to move on.
"We played a good game but we are suffering in this moment. We have to be stronger because we have the quality to come out from this difficult moment.
"I am sorry for the result and the [Cristian] Romero injury. I hope for us and for him that he it is not something important.
"We had three or four clear chances to score. Everything is tougher and we have to work in the style of play.
"We have to move on. We have to be stronger than this moment. I spoke with the players five minutes ago and said the same. It has been a tough season and we are going through a tough moment for everyone."
Story of the match in stats...
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Jamie Carragher believes Tottenham "look like they're going to go down" to the Championship after another dismal display in Roberto De Zerbi's first game in charge.
Spurs' 1-0 defeat at Sunderland means the club sit in the relegation zone with six games remaining and two-points off West Ham in 17th place.
Despite being one of the Premier League's so-called 'Big Six', their survival status in the top-flight is out of their hands.
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The result is damning but the performance was even worse. They created just 0.15 worth of Expected Goals in the second half against Sunderland, while a wasteful first half saw them miss 0.91 worth of xG overall - but failed to score.
"I can't believe it. Tottenham look like they're going to go down," said Carragher. "The other [relegation threatened] teams have something going for them."
Spurs now have six games to save their season in the midst of a long winless run. By the time they face Brighton next Saturday, live on Sky Sports, it will have been 111 days since they last tasted victory in the Premier League.
Spurs' remaining games include matches against fellow relegation rivals Wolves and Leeds - but Carragher believes they have "no chance" of beating even the Premier League's bottom club away from home.
"You look at fixtures, you think that's a good game for Tottenham. But they're awful. Tottenham's a good game for them.
"Wolves are bottom of the league. Do you think Tottenham will go there, and win? No chance."
O'Hara's explosive assessment of Spurs
If Carragher's assessment of Spurs' fate is damning, then former Spurs midfielder Jamie O'Hara's take is explosive.
"Absolutely shocking. Spurs didn't deserve anything from the game. It sums up Spurs this season. They did absolutely nothing, offered nothing.
"Non-existent performances all over the park. Connor Gallagher, shocking. Randal Kolo Muani, shocking. Dominic Solanke, shocking. Richarlison, shocking. Destiny Udogie, shocking.
"You can't carry six players when you are fighting relegation! You have to fight and put in a performance.
"Absolutely woeful again. I can't believe how bad this team have got. De Zerbi is a good manager but he can't produce miracles; the players have to produce for him.
"Nowhere near good enough. The quality on the pitch is non-existent. These players have fallen so far off from where they think they are as footballers.
"I am not seeing anything from this team that warrants staying in the Premier League. There is nothing that says they can stay up. There isn't enough fight, quality or passion.
"For the majority of the game, I couldn't believe what I was watching. These players are nowhere near it."
O'Hara has ranked Spurs' chances of Premier League survival at just "10 per cent" and believes De Zerbi is not able to work "miracles".
"They have not won this year," he added. "It will be April 18 next weekend and Spurs haven't won in the Premier League.
"Where are the points coming from? They need seven or eight points. Where are they coming from? I can't see it.
"The players are not good enough and are not producing. Pumped by Nottingham Forest and beaten by Sunderland. West Ham have got fight. Forest picked up another point. Leeds have fight and have energy at home.
"I don't see anything from Spurs to say they can get out of this. I cannot believe how bad this team have got.
"De Zerbi hasn't got the players. I think you could see a style of play from Tottenham; he knows what he is doing in terms of how he wants them to play.
"A slower build-up and possession-based. You could see what he is trying to do but you have to rely on the players to put in a performance.
"What can you do as a manager? You are waiting to get beaten as they are not producing quality on the pitch. There is not enough quality. The players, it's remarkable, the performances they are putting in at this stage of the season and what is on the line.
"Solanke, £60m Spurs paid for him! He was meant to be Harry Kane's replacement but it looks like he's forgotten how to play football.
"Solanke's performance today needs to be studied. It's one of the worst performances I've seen. It's remarkable some of the football I've seen. De Zerbi must be scratching his head.
"We don't deserve anything from the game - Kinsky was the best player! I couldn't believe what I was working. De Zerbi is not a miracle worker."
De Zerbi: One win changes everything
Reacting after the game, De Zerbi says Spurs have to be stronger as they are in a "bad moment" - but one win would change their season.
"We have to be stronger. I spoke to the players five minutes ago, and I said the same," De Zerbi told Sky Sports.
"I understand everything, I can understand it's been a tough season. We are going through a tough moment for everyone. But we have to react, we have to react with enthusiasm, the right spirit. They showed that today. I can't say anything about that.
"What we have to do is just work, just transfer what I think. I'm an honest man, I'm telling you what I think, what my opinion is. We have big players, now they are in a bad moment. There's results, the part of the season. But we have to work on one win. With one win, we can change everything this season.
"I have 24 hours in a day. It's not a problem of time. I want to find the right way to reach the heads of my players. I'm honest. When I say we created two or three chance in the first half with Udogie, Richarlison, Solanke - we did the same what we've done in the week. For that, the qualities of the players are great, but not enough.
"Now we have to believe more in ourselves and our team-mates. The crucial part is to win one game. One game, one game, one game.
"In terms of style of play, we can play much better than today. But after five or six training sessions, it's difficult. The problem is not a style of play, the problem is the mental part. Together we have to stay focused to win one game."
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