Skipper Nemanja Vidic and central defensive partner Rio Ferdinand are also set to be included for the Old Trafford encounter.
However, winger Ashley Young (knee) and defender Jonny Evans (hamstring) remain sidelined.
Southampton could welcome club captain Adam Lallana back into their side.
Saints' boss Mauricio Pochettino has confirmed Lallana trained with the squad during a trip to Barcelona and is in contention to be involved at Old Trafford after missing almost two months with knee ligament damage.
Jose Fonte and Guly Do Prado (both knee) are absent, but new signing Vegard Forren is in line to make his debut.