Manchester United winger Anthony Martial has been ruled out of the midweek clash with Crystal Palace, while Marcus Rashford remains a doubt.
The Red Devils will also be missing Nemanja Matic, Ander Herrera, Juan Mata and Jesse Lingard for the game at Selhurst Park, with interim manager Ole Gunnar Solskjaer confirming that United will be without ten first team players.
As a result, United are likely to include teenage trio Angel Gomes, James Garner and Tahith Chong in their squad as Solskjaer turns to youth to help him through this mini injury crisis.
"The three we had to take off [Herrera, Lingard, Mata], they're not going to be ready," Solskjaer told MUTV on Tuesday morning.
"As for Rashy [Marcus Rashford], we're going to work on him for as long as we can to see if he gets ready because that wasn't as bad as we first feared, so luckily I don't think we damaged it any more by him finishing the game," he added.
"He might have a chance of playing. Then again I don't think there'll be anyone else coming back for this game. So there'll be a chance for the kids."
Garner is still waiting for his senior debut but Solskjaer has already handed opportunities to Gomes and Chong, who appeared as substitutes in games against Huddersfield and Reading respectively. The trio were tellingly left out of the Under-23 game on Monday night.
"The two of them are good mates and they link up well together," the boss explained.
"So this might be a chance for them to find some form and give us a selection headache when everyone is fit again. Hopefully Alexis and Rom can step up."
Despite overcoming huge tests against Tottenham, Arsenal, Chelsea and Liverpool, as well as a learning curve against Paris Saint-Germain, this week's Palace game is arguably the biggest challenge yet for Solskjaer in light of the injuries.
It is crucial United win after being leapfrogged by Arsenal on Sunday in the race for the top four.