Harry Maguire, Edinson Cavani and Mason Greenwood are among five Manchester United players not to have travelled for their Champions League opener against Paris Saint-Germain.
Defender Eric Bailly and midfielder Jesse Lingard are also missing with injuries in a blow for Ole Gunnar Solksjaer ahead of the Group H clash at Parc des Princes on Tuesday.
New signing from PSG Cavani is not fit enough to play, having only trained with his team-mates for the first time on Sunday following a mandatory 14-day coronavirus quarantine after arriving in the UK - but he is in contention for Saturday's Premier League game against Chelsea.
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Bruno Fernandes, meanwhile, will captain the team in the absence of Maguire, manager Solskjaer has confirmed, after the England centre-back had made a step back to his best with a goal in the 4-1 win over Newcastle over the weekend.
"We hope the players won't be away for too long. Edinson needs a few more days training before we can think about the weekend," Solskjaer said in Paris on Monday. "Hopefully the same with Harry, Eric and Mason as well, but we're not sure about that."
Regarding Greenwood's injury, Solskjaer said: "It's just a niggle. As young as he is, we don't want to take any chances with him. Hopefully by the weekend, he'll be fine again."
Solksjaer also commented on his decision to leave first-team players Sergio Romero, Phil Jones and Marcos Rojo out of his squad for the Champions League group stage.
He said: "We had 25 to put on the list. Phil has been injured, Marcos has been injured and away from the team for a long time and Sergio has not come back to us yet.
"When we had to put the list in, we put the available players on."
Fernandes delighted by surprise captaincy
Solskjaer's decision to hand Fernandes the captaincy in the absence of Maguire seemed to catch the Portuguese midfielder by surprise as the pair answered questions together at the pre-match news conference.
The 26-year-old has impressed since arriving at Old Trafford in January and Fernandes says he will wear the armband with pride.
"I was not expecting this," said Fernandes. "I've known the same time as you.
"For me, it's an honour that I will be captain of my team-mates and of course being captain of Manchester United is an important achievement for me.
"But I think the captain is everyone - everyone needs to help, everyone needs to be a leader in their way.
"The leadership is different in every player, so tomorrow it will not be about me but about the team.
"Leading the team is every day - it's in the training ground, every training, every game. I think everyone is doing their job, their own job, to lead the team in the way they think is best."
Last season's Champions League ended in bitter disappointment for the Premier League's representatives.
Holders Liverpool crashed out in the round of 16, their fate sealed in a wild defeat to Atletico Madrid at Anfield. Tottenham, the previous year's runners-up, were outclassed by RB Leipzig at the same juncture, while Chelsea suffered a similar fate against Bayern Munich.
Manchester City and Manchester United join Chelsea and Liverpool as the quartet of Premier League teams who head into this year's competition, and they go into it knowing the tournament is one of the most open in recent memory.
Real Madrid are in a state of transition and Barcelona teetering on the brink of full-blown crisis following a tumultuous summer in which a disillusioned Lionel Messi tried to engineer his departure.
There is uncertainty around Italian heavyweights Juventus, too, after the appointment of Andrea Pirlo as head coach this summer.
PSG boss Thomas Tuchel insists Cavani still has a lot to offer United.
The 33-year-old Uruguay international, who left PSG at the end of June, signed a one-year deal with United earlier this month.
"They've got a great personality, like with many of the biggest players of the game," Tuchel said. "It's the same with Edi.
"Very polite, almost a bit shy. Hard, hard worker. He will be there in every training (session) first minute until last minute. Every game from first second until last second. You can totally rely on him.
"He's living for goals, living for scoring. When he scores, when he has the confidence, he's one of the (best) number nines in world football."