The Barclays Premier League leaders host Everton with a six-point lead at the top of the table, and will look to go better than the 3-3 draw at Goodison Park earlier in the season.
Chelsea moved into second in midweek with the 3-1 win at Birmingham, and will look to continue keeping the pressure on United with victory against West Ham United.
Liverpool welcome Birmingham to Anfield chasing fifth place and a spot in the Europa League, with the Blues looking to secure their top flight status.
Spurs are themselves in pursuit of a team, with Manchester City in their sights. West Bromwich Albion are the visitors to White Hart Lane.
Aston Villa, fresh off a crucial win at Upton Park, will be hoping to provide some cheer to the hospitalised Gerard Houllier when Stoke City travel to Villa Park.
Elsewhere, and Wolves face Fulham, Blackpool visit Newcastle and Sunderland play Wigan. Arsenal face Bolton on Sunday, while Manchester City will play Blackburn Rovers on Monday.