The clash is now set to kick-off at 2pm on Sunday and has been rescheduled due to a television pick affecting Spurs earlier in the week.
Tottenham's meeting with Chelsea will be televised by Sky Sports on Thursday, April 3, meaning the Saints fixture has been moved back.
A Saints statement said: "Ticket information for the trip to Tottenham Hotspur Stadium will follow in due course."
While Saints are bottom of the Premier League with nine points and set for relegation, Spurs have also been enduring a difficult season.
The London outfit, under the management of Ange Postecoglu, are 13th in the league and only the bottom four have lost more matches (14).
However, Tottenham were 5-0 winners at St Mary's in September in former manager Russell Martin's final match as boss on the south coast.
No Saints matches have been selected for broadcasting in the April round of fixtures, with dates for those picks all confirmed this afternoon.