The Red Devils' recent resurgence came to a halt with a 1-1 draw against Wolverhampton Wanderers at the weekend, and now focus switches to a competition that they last won two seasons ago.
Here, Sports Mole looks at how the Portuguese may set out his side at Old Trafford.
Assuming Mourinho gives Romelu Lukaku the night off, with the Belgium international starting six of United's first seven games this term on the back of a busy summer, there is a central-striking role up for grabs.
Mourinho has already confirmed that Diogo Dalot will make just his second start for the club, a week on from an impressive debut in the away win at Young Boys, and on the opposite flank Ashley Young is expected to return after a two-game absence in place of Luke Shaw.
Ander Herrera has shaken off a minor injury problem in time for this third-round tie, but Mourinho may not want to risk the Spaniard from the off, as Nemanja Matic is back from suspension and both Andreas Pereira and Scott McTominay are in need of minutes on the field.