Wayne Rooney, Michael Carrick, Nemanja Vidic, Patrice Evra and David de Gea are all set to return after sitting out Sunday's shock FA Cup home defeat by Swansea.
Robin van Persie (thigh) and Phil Jones (knee) are unlikely to be involved. Marouane Fellaini (wrist), Ashley Young (shoulder) and Nani (hamstring) are definitely out, Fabio starts a three-match ban and Rio Ferdinand faces a spell on the sidelines after injuring his knee at the weekend.
John O'Shea returns to the Sunderland squad.
The Republic of Ireland defender has missed the last four games with a shoulder injury, but resumed training late last week and is in contention to start the first leg at the Stadium of Light.
O'Shea's back four colleagues Valentin Roberge and Modibo Diakite have recovered from the knocks which kept them out of Sunday's 3-1 FA Cup third round victory over Carlisle, but goalkeeper Keiren Westwood (shoulder) and defender Carlos Cuellar (hip) remain on the sidelines.
Sunderland (from): Mannone, Pickford, Celustka, Dossena, Alonso, Bardsley, O'Shea, Brown, Diakite, Roberge, Cattermole, Cabral, Gardner, Ki, Giaccherini, Johnson, Larsson, Ba, Karlsson, Mavrias, Colback, Fletcher, Altidore, Borini.
Manchester United (from): De Gea, Lindegaard, Smalling, Rafael, Evans, Vidic, Evra, Buttner, Valencia, Anderson, Giggs, Carrick, Cleverley, Fletcher, Kagawa, Zaha, Rooney, Hernandez, Welbeck, Januzaj.