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Varane started for his country in their Nations League final clash with Spain on Sunday night, but limped off late in the first half of the controversial 2-1 victory in Milan.
United anxiously awaited the results of a scan on the 28-year-old, who moved to Old Trafford from Real Madrid in a high-profile £41million deal in August.
The club have now announced that Varane will be sidelined for multiple weeks with the issue, missing Saturday’s Premier League trip to Leicester.
He will also miss the Champions League visit of Atalanta next Wednesday, as well as the clash with rivals Liverpool on October 24.
Ole Gunnar Solskjaer’s side then travel to Tottenham on October 30 before their return Group F fixture against Atalanta in Italy three days later.
United face a Manchester derby against reigning champions City on November 6, capping a tough run of fixtures.
“Raphael Varane sustained a groin muscle injury in the UEFA Nations League final and has commenced rehabilitation at the club,” the Red Devils confirmed on Tuesday.
“He will be out for a few weeks.
“Everybody at United would like to wish Raphael a speedy recovery.”
Varane’s injury comes at a time when centre-back partner Harry Maguire has been sidelined with a calf injury suffered in the 1-0 defeat by Aston Villa on September 25 that ruled him out of the subsequent draw with Everton and England’s latest World Cup qualifiers against Andorra and Hungary.
Solskjaer has been reluctant to place a time frame on Maguire’s recovery and it remains to be seen if he will be fit to play against Leicester.
However, further forward, Marcus Rashford and Amad Diallo could be back in the first-team picture after recovering from shoulder surgery and a thigh injury respectively.