Ruben Amorim said he's expecting Bruno Fernandes to be out for a "while" after picking up an injury during Manchester United's 2-1 loss to Aston Villa on Sunday.
Fernandes appeared to pull up holding his hamstring at the end of the first half at Villa Park.
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He carried on until halftime, but was eventually replaced with Lisandro Martínez.
"I think it's soft tissue, so it's going to be a while," said Amorim. "I think he's going to lose some games, I don't know for sure so let's see. You never control these things so we'll see. He's a guy who is always fit so he can recover quite well but I don't know."
Losing Fernandes would represent a major blow for Amorim, who is already without Bryan Mbeumo, Amad Diallo and Noussair Mazraoui while they're at the Africa Cup of Nations.
Matthijs de Ligt and Harry Maguire are both injured while Kobbie Mainoo was a late withdrawal from the squad to face Villa after picking up a calf problem in training.
A lack of other options meant Amorim was forced to hand senior debuts to 18-year-old pair Jack Fletcher and Shea Lacey at Villa Park.
"I think he [Fernandes] is not going to play for a few games, but we'll see," he said. "Last year we had the same situation at this time so it is not going to kill us, it is going to make us stronger. The kids did well today, and we have to work with the players that we have, no excuses, and try to win the next one."
United are next in action against Newcastle at Old Trafford on Boxing Day and if Fernandes misses the game, it will be just the third time he's been sidelined with injury or illness since moving from Sporting CP in January of 2020.
He missed one game with the flu in March of 2022 and two games because of a knee injury in May 2024.
"It's massive," said defender Diogo Dalot. "We don't know how bad it is but for him to come off, we know how tough he is. Hopefully it's not too bad and we keep with him for the next games.
"This is the time that opportunities come for other players and the time you step up and show you deserve to be in the team and play more minutes.
"I think that's how the players who get opportunities should look at it. We are Manchester United and we have to find a way to win."