Manchester United have confirmed that Raphael Varane suffered a hamstring injury during Wednesday's Champions League clash with Atalanta BC in Italy.
The France international recently missed three games for the Red Devils due to a muscular problem that he suffered while representing his country last month.
However, the 28-year-old is now facing another month on the sidelines, meaning that he could be absent for five key matches for the 20-time English champions.
Varane showed his class in Man United's 3-0 win over Tottenham Hotspur in the Premier League last weekend, with the World Cup winner helping his side keep a rare clean sheet in North London.
The centre-back has made nine appearances for Ole Gunnar Solskjaer's side this term but is now not expected to be seen in a red shirt until the early stages of December.
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Varane will definitely be absent against Manchester City in the Premier League this weekend, while Victor Lindelof is still a doubt due to the problem that forced him to miss out against Atalanta, meaning that Eric Bailly could start alongside Harry Maguire in the middle of the defence.
The Frenchman will also sit out the trip to Watford on November 20, in addition to the key Champions League contest against Villarreal on November 23, where Solskjaer's side will be looking to secure their spot in the last-16 stage of the competition with a match to spare.
Crucially, unless something drastic changes, Varane will miss the trip to league leaders Chelsea on November 28, in addition to the home match against a revitalised Arsenal on December 2.
Realistically, the former Real Madrid defender has a chance of recovering for the home game against Crystal Palace on December 5, which comes ahead of the team's final Champions League group-stage contest against Young Boys three days later.
Varane's absence against Man City, Chelsea and Arsenal could prove particularly damaging, with Man United already conceding 15 times in the Premier League this term, which is more than the likes of Crystal Palace, Brentford, Southampton, Brighton & Hove Albion and Wolverhampton Wanderers.