Luke Shaw was reportedly not with the Manchester United squad that arrived at their pre-match hotel for Wednesday's Champions League clash with Villarreal.
The England international had to be replaced in the first half of Saturday's 1-0 loss to Aston Villa in the Premier League, having suffered a muscular problem.
During Tuesday's pre-match press conference, Man United boss Ole Gunnar Solskjaer said that the left-back had a chance of being involved against the Yellow Submarine.
However, according to Manchester Evening News journalist Samuel Luckhurst, the defender was not with the squad that arrived at the pre-match hotel on Wednesday afternoon.
The Red Devils will also definitely be missing Aaron Wan-Bissaka through suspension, while club captain Harry Maguire is facing a period on the sidelines with a calf problem.
As a result, Diogo Dalot, Alex Telles, Eric Bailly and Victor Lindelof are all in contention to feature alongside Raphael Varane in defence for the home side against their Spanish opponents.