It's a third different competition in a week for United as Louis van Gaal's side welcome Championship high-flyers Boro' to Old Trafford with a place in the last eight of the League Cup at stake.
Middlesbrough sit fourth in the second tier- having been 90 minutes away from a top-flight return last season (only to lose the play-off final to Norwich), and are led by Jose Mourinho's former protege Aitor Karanka.
The visitors boss has hinted that he may ring the changes to prioritise another promotion push, and his United counterpart has said that he may do the same.
"I am yet to decide on my selection, because I have several players in the "red zone" as we have had a lot of matches to play.
"I have to see if I can use them or not so I shall decide on Wednesday, we need all the days to recover and some players recover better, so it is difficult to say my selection.
"I shall consider using some of the young players but you have to wait and see."
Antonio Valencia has been ruled out with the foot injury that forced him in the derby, and Luke Shaw and Paddy McNair remain injury absentees.
James Wilson and Ashley Young are both close to a return and so could feature, whilst Andreas Pereira could be in line for another start after his impressive display against Ipswich in the last round.
Van Gaal added:
"Yes of course they (Pereira and Wilson) are in the squad, but I have to select the line-up and that I don't know- I have to do that on Wednesday"
United's Spanish playmaker Juan Mata said that he and his Reds team mates are looking for a run to the final in the Capital One Cup.
"Middlesbrough are playing in the Championship, but last season they were very close to being promoted to the Premier League and they are up there again this year so it's going to be a good test for us.
"I've never won this competition before and neither have many of our team, and we always want to be winning trophies, so I hope we can do that this season"
Form guide: United W W L W D D Middlesbrough W W L D L W
Match odds: United 21/50 Draw 9/2 Middlesbrough 32/5
Referee: Lee Mason, from Lancashire, takes charge of this one.