Paul Pogba will undergo surgery on a recurring ankle injury and is expected to spend another month on the Manchester United sidelines.
The World Cup winner's latest setback was confirmed by manager Ole Gunnar Solskjaer after his side's crushing 2-0 defeat at Arsenal.
Pogba made his comeback after nearly three months out in a 2-0 defeat at Watford 10 days ago and also made an appearance off the bench in a 4-1 thrashing of Newcastle four days later.
"We've had scans and it's nothing major, it's something that has to be sorted and dealt with. He's been advised to it as soon as," said Solskjaer.
Pogba has made just six starts in all competitions for United this season and his influence in midfield has been badly missed with United sitting fifth in the Premier League.
His latest setback comes at a bad time for Solskjaer with Scott McTominay also sidelined for two months leaving the Norwegian extremely short on midfield options.
"It's a big blow that Paul is out now that Scott's out, he'll be out for a few months. Paul will be back within a month."
Speculation also surrounds Pogba's future at Old Trafford after he expressed a desire to leave the club before the start of the season.
Real Madrid reportedly remain interested in the man who cost United a then world record £89 million (Dh433m) in 2016, but no move is expected to be made in the January transfer window.
And Solskjaer denied suggestions it is Pogba's own medical team rather than the club's which has suggested to undergo surgery at this time.
"We look after our players' health," added Solskjaer. "It's been advised that he should do it as soon as possible."
Arsenal earned their first win under new coach Mikel Arteta by comprehensively overpowering a stale United with goals from Nicolas Pepe and Sokratis.
Club record signing Pepe put Arsenal ahead in the 10th minute of their third game under their former player by lashing into the net after good work down the left flank from Sead Kolasinac.
Pepe later hit the post in a dominant first-half display from Arsenal before defender Sokratis deservedly doubled their lead in the 42nd minute by pouncing on some hesitant defending from the visitors following a corner. Arsenal comfortably saw out their advantage to record a first league win in five games which took them up to 10th in the standings on 27 points after 21 games.
Solskjaer's side remain fifth on 31 points after missing out on the chance to narrow the gap on fourth-placed Chelsea.
"I think it was great. We were great in the first half and showed a maturity in the second," said Arsenal defender David Luiz.
"Mikel Arteta is a great coach, he was a great player. I think he can improve every player. Our season started very bad but things can change."
United were searching for a third consecutive win but were out-fought by Arsenal and rarely looked capable of staging a revival, even after Mason Greenwood and Andreas Pereira came on and injected some energy into their attack.
"They played with high intensity, aggression and passed the ball way better than us," said United defender Harry Maguire.
"The second goal was disappointing, we are conceding far too many from set plays. We need to do the basics. And to lose the second gave us too much to do in the second half. We huffed and puffed but it wasn't good enough."
Once considered the Premier League's showpiece fixture when the clubs routinely battled for the title but, United and Arsenal now find themselves caught up in a topsy-turvy campaign.
The Gunners looked far more assured in defence than they have all season and were quick to snuff out United's attackers whenever they advanced towards their area.
"We have started again, I think we have a lot of space to improve," added goalscorer Sokratis.
"The second half we didn't play like the first but I think every game we are getting better. The fun is back."