Seville - Jose Mourinho fears Ander Herrera has a "bad injury" after the Spanish midfielder was forced off in the first half of Wednesday's 0-0 draw with Sevilla in the Champions League.
Herrera hadn't played in United's previous three matches due to a muscle injury before being recalled for the last 16, first leg at the Sanchez Pizjuan.
However, he lasted only 17 minutes before being replaced by Paul Pogba.
"I think it's a bad injury. He had a small injury that stopped him for the last couple of matches, but the medical department gave him 100% ready for last Saturday," said Mourinho after the game in Spain.
"We didn't play him to give him more work and more protection but it looks like he wasn't fully fit."
Mourinho added: "He looked fit and the way he was playing during the time he was on the pitch - he was pressing a lot, really high - you only do that when you feel good.
"Then it was a back-heel and a back-heel creates a contraction in the muscular area where he had the biggest problem, and now we have proof that he was not 100% fit."
United were reliant on some fine David de Gea saves to leave the Sanchez Pizjuan with a draw, but the result leaves the tie wide open ahead of the return at Old Trafford next month.
"We have to decide it at Old Trafford," Mourinho added.
"Last season we had Europa League knockout games there which obviously is not the same.
"In previous years we were out in the group phase, so Old Trafford needs a big Champions League night."
The return leg is scheduled for Tuesday, March 13.