Ruben Amorim's Reds face a third away league game since the turn of the year, following the 2-2 draw at Liverpool and 1-0 victory at Fulham.
Spurs currently sit one place and two points behind United in the table, in 14th spot, with both teams experiencing difficult top-flight campaigns. While we progressed in the Emirates FA Cup last time out, Ange Postecoglou's men crashed out at Aston Villa.
The two English sides in the Europa League can only meet each other in the final in Bilbao, as the Reds and north Londoners await the outcome of the play-offs in the competition.
Having lost to Spurs 3-0 at home, when Bruno Fernandes was sent off in the first half - his red card was later overturned - and then 4-3 at the Tottenham Hotspur Stadium in the Carabao Cup, there will be a real determination to set the record straight in the capital.
HOW TO WATCH AND FOLLOW
The Tottenham Hotspur Stadium clash will take place on Sunday at 16:30 GMT. MUTV's build-up starts at 15:25 GMT, while Sky Sports are covering the match action live in the UK.
You can listen along to the game through our radio commentary, with pre-match and post-match coverage also on offer, live from the ground.
As always, you can tune in via ManUtd.com and the United App, where our match centre will have rolling updates, opinions and stats across the 90 minutes, as well as the highlights two hours after the final whistle.
Longer versions will be made available from Monday.
TEAM NEWS
Lisandro Martinez joined Luke Shaw, Jonny Evans and Mason Mount on the sidelines after suffering a knee injury in the recent defeat to Crystal Palace.
Under-21s goalkeeper Hubert Graczyk was on the bench for the cup win over Leicester City, as Altay Bayindir and Tom Heaton were both unavailable.
Patrick Dorgu made his debut against the Foxes, coming off at half-time, while Ayden Heaven was close to his bow after being an unused substitute.
Richarlison appears to have joined a lengthy injury list for Spurs, which includes Radu Dragusin, who is out for the season. However, manager Postecoglou has suggested he will welcome a few players back into contention for this weekend's encounter.
Guglielmo Vicario, Destiny Udogie and James Maddison are among those tipped to return, while influential defenders Cristian Romero and Micky van de Ven are believed to be not too far away from being fit enough to play.
OPPOSITION REPORT
Spurs are experiencing a tough time of things, with an impressive 2-0 victory at Brentford their only league win this year. Their last home outing in the competition was the surprise 2-1 reverse to Ruud van Nistelrooy's Leicester City in January.
Postecoglou has, rightly, pointed to the long injury list as the main source of the problems but the attack was strengthened during the window, when Mathys Tel arrived on loan from Bayern Munich. The promising striker got off the mark with the consolation effort in the 2-1 FA Cup loss at Villa.
With Dominic Solanke, who has a good record against United, another of those out of action at the moment, Tel could be a key figure on Sunday.
Centre-back Kevin Danso has also joined to help increase the options in defence.
DID YOU KNOW?
Amorim's side are looking to prevent Tottenham completing their first league double over the Reds since the 1989/90 season.
In that campaign, the north Londoners also knocked Alex Ferguson's team out of the League Cup, winning 3-0 at Old Trafford.
Gary Lineker scored the only goal of the league game at the Theatre of Dreams, before adding to a Paul Gascoigne strike to claim the eventual winner in a 2-1 triumph at White Hart Lane. Steve Bruce's penalty pulled one back for the visitors.