With Aaron Wan-Bissaka struggling with injury, Ole Gunnar Solskjaer turned to Victor Lindelof in the position against Leicester on Boxing Day but the Swede was forced off midway through the second half with a knock of his own.
Axel Tuanzebe could be in line to fill the void, with Eric Bailly partnering Harry Maguire at centre-back.
Further forward, Solskjaer is likely to shuffle his pack given the short turn around, though his side should be fresher than Wolves, who only played against Tottenham on Sunday night.
Alex Telles, Donny van de Beek, Nemanja Matic and Mason Greenwood were among those who did not feature against the Foxes, while Paul Pogba and Edinson Cavani made only substitute appearances.
Man Utd predicted XI: De Gea; Tuanzebe, Maguire, Bailly, Telles; Matic, Pogba, Fernandes; Greenwood, Rashford, Cavani