Ole Gunnar Solskjaer is likely to make six changes to the side that beat Watford 3-0 on Sunday for the visit of Club Brugge on Thursday evening.
The second leg fixture is nicely poised following the 1-1 draw in Belgium last week and the Manchester United boss is set to rotate his players ahead of a busy run of games.
United face trips to Everton in the league then Derby County in the FA Cup fifth round before facing off against local rivals Manchster City at Old Trafford next Sunday.
So it is no surprise to see fresh legs introduced to the side that dominated the Hornets at Old Trafford.
The biggest change sees United revert from the back four used at the weekend to a system with three central defenders, as used in the first leg at Brugge.
This means Luke Shaw will tuck in from full-back and youngster Brandon Williams has another chance to impress in the wing-back role.
Elsewhere, defensive stalwart Aaron Wan-Bissaka will drop to the bench in favour of Diogo Dalot, while Harry Maguire and Victor Lindelof will continue their formidable partnership at centre-back.
In goal, Sergio Romero is set to replace David de Gea, as he has done for the bulk of United's cup duties this season.
In midfield, Bruno Fernandes will operate in a deeper role than he did at the weekend – when he impressed by picking up a goal and an assist – and he will combine with Scott McTominay and Juan Mata.
This will be McTominay's first start since suffering a knee injury on Boxing Day, and the Red Devils were grateful to welcome back the midfielder as a substitute at the weekend.
Up front, in-form Anthony Martial has a chance to score in his fourth game in a row and will partner Jesse Lingard.
Lingard was omitted from the squad at the weekend and faces stiff competition for a spot in the United attack from Mason Greenwood.
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