Ole Gunnar Solskjaer is set to make six changes from the side that beat Chelsea for their Europa League clash with Club Brugge.
United travel to Belgium for the first leg of the last-32 tie on Thursday, just a few days after their crucial win at Stamford Bridge.
And Solskjaer will use the fixture as an opportunity to rest some legs and freshen up his starting XI.
Victor Lindelof will be recalled into the heart of United's defence after missing Monday's fixture with an illness.
That means Eric Bailly will drop to the bench despite his heroics on his return from injury, and he'll be joined by Aaron Wan-Bissaka.
Full-back Wan-Bissaka was instrumental in United's victory over the Blues, setting up Anthony Martial's opener, but makes way for the Brugge clash to give Diogo Dalot a chance to impress.
Youngster Brandon Williams will also be afforded some respite from the rigours of first-team action, with Andreas Pereira due to come into the side.
That suggests United will revert to four at the back, with Luke Shaw and Harry Maguire keeping their places in the team.
Pereira will be joined in midfield by Juan Mata - who replaces Fred - alongside Nemanja Matic and Bruno Fernandes.
At opposite ends of the pitch, Sergio Romero continues his Europa League involvement in favour of David de Gea, while Martial leads the line in attack.
There's also a place in the side for Jesse Lingard, who is preferred in favour of Daniel James.
Solskjaer has recently been urged to drop James by Sky Sports pundit Paul Merson.
"With Manchester United , you're talking about one of the biggest clubs in the world not having a centre forward," Merson told Sky Sports.
"They're playing with Daniel James up front, who sooner or later has to be taken out of the team. You feel sorry for the lad, now. He looks a bit lost if I'm honest – he needs a break."
Here's how United could line up against Club Brugge...
Man Utd predicted lineup (4-2-3-1): Romero, Dalot, Lindelof, Maguire; Shaw; Pereira, Matic; Mata, Fernandes, Lingard; Martial
