Wayne Rooney returns to the United squad.
Rooney has not featured since a brief substitute appearance against West Brom at the beginning of last month but is now on the verge of a full recovery from his ankle injury and eager to get his first goal in open play since March.
Rio Ferdinand (hamstring) and Chris Smalling (groin) returned from international duty with minor injuries, while Ryan Giggs (hamstring) is also a doubt.
Defender Gary Caldwell will miss out for Wigan with a thigh problem.
Manager Roberto Martinez expects the Scot could miss as many as six weeks with the injury, with fellow centre-half Emmerson Boyce also out with a muscle problem.
Caldwell's brother Steven could be drafted into the side, while James McCarthy is a long-term absentee with an ankle injury.
Victor Moses is pushing for a start at Old Trafford after coming off the bench to hit the winner against West Brom last weekend.
United (from): Van der Sar, Kuszczak, Brown, O'Shea, Ferdinand, Vidic, Smalling, Evans, Evra, Fabio, Obertan, Bebe, Carrick, Gibson, Fletcher, Anderson, Nani, Park, Berbatov, Rooney, Hernandez, Macheda.
Wigan (from): Al Habsi, Stam, Gohouri, Alcaraz, Figueroa, Thomas, Diame, N'Zogbia, Gomez, Rodallega, Kirkland, Di Santo, Moses, McArthur, S Caldwell.