Against Everton in the Premier League, the World Cup winner was substituted after a thigh injury and has subsequently missed games against West Ham and West Brom.
The Red Devils only defeated West Ham 1-0, while they were uninspiring in a 1-1 draw versus West Brom, which highlights their need to get Pogba back as quickly as possible.
He could be set to miss another two weeks of action, though no confirmation has been given on a return date.
Dean Henderson should come in to replace David De Gea for this one, and it is probably just as much on merit as it is that he has been United's cup goalkeeper this campaign.
There could be a couple of changes at the back, with Alex Telles and Eric Bailly coming in for Luke Shaw and Victor Lindelof respectively. Aaron Wan-Bissaka and Harry Maguire should retain their places from the weekend.
Nemanja Matic is pushing for a start, but Ole Gunnar Solskjaer will likely stick with Fred and Scott McTominay in the middle of midfield.
There will be no Donny van de Beek or Edinson Cavani, with Solskjaer confirming on Wednesday that neither player had travelled with the squad.
Marcus Rashford will start on the left, Mason Greenwood on the right, and Anthony Martial up top.