Alexis Sanchez was forced off injured during Manchester United's Premier League clash with Southampton at Old Trafford on Saturday.
With Ole Gunnar Solskjaer's men trailing 1-0 early in the second half, the Chile international appeared to hurt his knee in a collision with Jan Bednarek in the Saints box. He was immediately replaced by Diogo Dalot.
It was a blow that appears to put the former Arsenal attacker's participation in Wednesday's Champions League last-16 second leg against Paris Saint-Germain at Parc des Princes in grave doubt.
The Red Devils have been luckless on the injury front in recent weeks, losing Anthony Martial and Jesse Lingard to muscular injuries in the first leg against PSG before Solskjaer was forced to make three changes in the first half of last weekend's scoreless home draw against Liverpool.
Marcus Rashford was one of the players to suffer against the Reds but was able to return to action from the outset of the Saints match, but neither Martial or Phil Jones, who were doubts prior to the encounter, were able to make the bench.
Meanwhile, Solskjaer was forced to do without six first-team squad members, including midfielders Nemanja Matic, Ander Herrera, Lingard and Juan Mata.
With Sanchez also facing a spell on the sidelines, it promises to be a depleted squad that he takes to the French capital.
On a personal note, it is just the latest blow for the 30-year-old, who has struggled to justify his £350,000-per-week ($462,000) wage since arriving from Arsenal in the transfer window of January 2018.
In 41 matches for United, he has scored only five goals and produced another nine assists, while he has performed well below the standards he set with the Gunners, where he netted 80 times in 166 outings.
Indeed, within 10 minutes of the Chilean going off at Old Trafford, United had raced into a 2-1 advantage, with goals arriving from Andreas Pereira and Romelu Lukaku before Southampton drew level through James Ward-Prowse.
The Red Devils have been in fine form since Solskjaer took charge, suffering only a single defeat in the 15 matches he has overseen.
Such form has brought the club back into contention for a top-four finish, with Arsenal's 1-1 draw with Tottenham earlier on Saturday to their benefit.