Dimitar Berbatov and Darron Gibson both drop to the bench with Javier Hernandez and Paul Scholes coming in to replace them.
United are set to line-up in a 4-3-3 formation with Hernandez playing down the centre as the lone striker with Nani out to his right while Wayne Rooney moves to the left flank.
Wigan boss Roberto Martinez has gone for the same line-up that featured in the last Premier League fixture that earned them a vital point at Anfield against Liverpool.
Hugo Rodallega looks set to be the lone front man in a 4-5-1 formation, which could convert to a 4-3-3 formation during the game, and Victor Moses and Charles N'Zogbia on the right and left flanks respectively.
Wigan Athletic: Al Habsi; Gohouri, Alcaraz, Caldwell, Figueroa; McCarthy, Diame,Watson, N'Zogbia, Moses; Rodallega,
Subs: Pollitt, S. Caldwell, Thomas, Di Santo, Gomez, McArthur, Lopez.
Manchester United: Van der Sar; O'Shea, Smalling, Vidic, Evra; Scholes, Carrick, Fletcher; Nani, Hernandez, Rooney
Subs: Kuszczak, Brown, Berbatov, Fabio, Rafael, Gibson, King.