Ruben Amorim fears Bruno Fernandes will be out for "a while" after the Manchester United captain was injured during Sunday's 2-1 defeat against Aston Villa.
Fernandes has started every Premier League game this season, but the Portugal midfielder is unlikely to extend that run any further following his injury setback at Villa Park.
The 31-year-old initially played on after pulling up with what appeared to be a hamstring issue just before the break, but he did not return for the second half.
Amorim ruled his influential star out of the Boxing Day clash against Newcastle, with severe doubts about his availability for the rest of the Christmas and New Year schedule.
"It's a soft tissue. I think he's going to lose some games. I don't know for sure, so let's see," Amorim said.
"You never control these things, so we'll see. He is a guy who is always fit so he can recover quite well, but I don't know."
Fernandes' fitness blow compounded Amorim's injury problems, with England midfielder Kobbie Mainoo missing the Villa game due to a calf issue.
The 20-year-old had dominated the build-up to Sunday's game after his half-brother wore a "Free Kobbie Mainoo" t-shirt to Monday's 4-4 draw with Bournemouth at Old Trafford.
Mainoo would have been in contention to make his first Premier League start of the season against Newcastle, but instead he is set to miss out.
"I will see what we are going to do," Amorim said. "I think Kobbie Mainoo is out, Bruno is out, so we will see. We are going to find solutions. No excuses.
"We need to win the next game and we will try to win the next game."
While Casemiro will return from suspension against Newcastle, Bryan Mbeumo, Amad Diallo and Noussair Mazraoui are at the Africa Cup of Nations and Matthijs de Ligt and Harry Maguire are also sidelined.
United's selection crisis has raised questions about the potential for new signings during the January transfer window, but Amorim won't panic.
"We need to deal with that," he said. "What we cannot do is to reach January and try to do everything in urgency and make mistakes and then 'here we go again' with a lot of mistakes.
"I'm not going to say 'we need a lot of players' because we have a plan. If we have to suffer, the club comes first.
"Of course, we are in a moment where we need points, but we need to find solutions and we are going to continue with our plan."
