Ferdinand only made the bench at Everton on Saturday but with skipper Nemanja Vidic suspended, Sir Alex Ferguson will be forced to field yet another central defensive formation.
Ryan Giggs (hamstring), Ashley Young (toe) and Chris Smalling (foot) miss out, along with Tom Cleverley (ankle).
Cleverley limped out of the weekend win at Everton after hurting his ankle.
And while Ferguson does not believe the damage is too extensive, he is not willing to risk further injury.
"Tom won't play tomorrow," said Ferguson.
"It is not serious. He got a little tweak on Saturday but we have to take the long view.
"We need to make sure he will be available for a long period, rather than play him again and the decision comes back to haunt us, so I think he will miss the Saturday game also."
United (from): De Gea, Lindegaard, Amos, Jones, Rafael, Fabio, Ferdinand, Evans, Evra, Freyes, Cole, Pogba, Valencia, Anderson, Park, Fletcher, Gibson, Nani, Diouf, Hernandez, Owen, Rooney, Berbatov, Welbeck.