United incredibly lost three players to injury in the first half alone against Liverpool, leaving Ole Gunnar Solskjaer with a depleted squad for the quick turnaround in fixtures.
The Norwegian remains unbeaten in domestic action as interim United boss, though, and here Sports Mole looks at how he could line his side up for the match.
Out: Nemanja Matic (muscle), Ander Herrera (hamstring), Jesse Lingard (hamstring), Juan Mata (hamstring)
Doubtful: Anthony Martial (groin), Marcus Rashford (ankle), Matteo Darmian (knock), Antonio Valencia (muscle), Marcos Rojo (knock)
The injuries have really begun to pile up for United following that remarkable first half at Old Trafford on Sunday, and the bulk of Solskjaer's problems come in midfield.
Herrera, Mata and Lingard - the latter of whom was himself a replacement for Mata - all limped off in the opening 45 minutes with hamstring injuries and could be set for a few weeks on the sidelines.
Those troubles came after Matic had been ruled out of the contest altogether with a muscle injury of his own, and he will not recover in time for Wednesday's trip to Selhurst Park.
Solskjaer trusted both Scott McTominay and Andreas Pereira above Fred for the Liverpool game and is likely to do the same again in midweek, although the busy schedule could help Fred's hopes of being handed at least some game time.
Anthony Martial is another who missed the Liverpool game and he remains a doubt for Wednesday, although he is regarded as more likely to feature than Rashford, who Solskjaer admitted he should have taken off in the fifth minute of the match agaist Liverpool after his ankle began to swell up.
Rashford went on to play the full 90 minutes, but his manager said that he would be "surprised" if he is in the starting lineup again at Selhurst Park, leaving space for Romelu Lukaku and Alexis Sanchez in the front three.
The one area which could remain untouched is the defence, which held off Liverpool's attack on Sunday as David de Gea claimed his 100th Premier League clean sheet.