Raphael Varane suffered a hamstring injury that forced him out of Manchester United's Champions League draw with Atalanta.
The 28-year-old was replaced in the first half after he sat down on the pitch and asked for treatment.
Varane only returned from a groin injury at Tottenham on Saturday and he played in the middle of a back three in that victory in North London.
That was a role he reprised against Atalanta but he lasted only 38 minutes before being replaced by Mason Greenwood as Ole Gunnar Solskjaer switched to a back four.
United were already without Victor Lindelof, who picked up a minor knock in training on Monday, and they will now be sweating on the fitness of Varane ahead of the Manchester derby.
Speaking after the game, Solskjaer said United felt they couldn't take a risk by leaving Varane on the pitch.
"He felt his hamstring - you can't take any risks. He’s been such a calming influence and then we’ve lost him, but that's football," said the United boss to BT Sport.
United were 1-0 down when Varane went off and in his absence Harry Maguire and Eric Bailly played together in a back four. Cristiano Ronaldo equalised on the stroke of half-time and although Duvan Zapata restored United's lead, Ronaldo struck again in stoppage time.
