The club has revealed that Maguire has sustained a muscle injury in training.
The centre half will now be out for the coming weeks and could struggle to make the FA Cup final.
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Victor Lindelof, Raphael Varane, Willy Kambwala and Lisandro Martinez are all injured as well.
United have only Diogo Dalot and Aaron Wan-Bissaka as fit senior defenders, with Jonny Evans possibly available.
The Red Devils take on Crystal Palace in the league on Monday night, as they look to get back to sixth place in the table.