France's World Cup-winning defender Raphael Varane's hopes of playing in this year's finals diminished on Wednesday as Manchester United manager Erik ten Hag said he will not play before the tournament gets under way on November 20.
The 29-year-old left the pitch in tears with a leg injury during United's 1-1 draw against Chelsea last Saturday.
"Varane isn't in the squad," said Ten Hag on the eve of United's Europa League match with Moldovan side Sheriff Tiraspol.
"He will be out until the World Cup. We have to see how he develops, how his rehab will develop."
The other significant development was the inclusion of Cristiano Ronaldo in the squad.
Ronaldo had been training away from the team towards the end of last week and was left out of the squad for Saturday's trip to Chelsea after being dropped for refusing to go on as a substitute against Tottenham Hotspur in their previous match.
The Portuguese star, 37, rejoined the group on Tuesday, providing a welcome boost for United in attack with Anthony Martial still sidelined after missing their last four games due to a back problem.
"Cristiano will be in the squad tomorrow," Ten Hag said. "It was not difficult. We said everything and we answered all the questions last week. So he was out for one game and now he is back in the squad as usual."
Ronaldo's actions have been an unwanted distraction during Ten Hag’s short reign at United after the Portuguese star failed to secure a summer transfer to a team playing in the Champions League.
While Ten Hag has said Ronaldo remains in his plans, there are still doubts over whether he can play a key role in the team.
Varane's injury, meanwhile, had added to the headaches of Ten Hag and France coach Didier Deschamps.
N'Golo Kante, Chelsea's defensive midfielder who was a key part of France's success four years ago, will definitely miss the tournament with a hamstring injury.
Paul Pogba is a doubt as he is still recovering from knee surgery and AC Milan goalkeeper Mike Maignan, the backup to first choice Hugo Lloris, could be ruled out with a calf injury.
Meanwhile, Ten Hag said he will make a late call on the availability of captain Harry Maguire, Donny van de Beek and Aaron Wan-Bissaka, all of whom also returned to training on Tuesday following their injury layoffs.
Varane's injury is a blow that may be offset by the return of United captain Maguire, who was out with a muscle injury sustained in England's 3-3 draw with Germany a month ago.
United are second in Group E on nine points, three behind leaders Real Sociedad, while Sheriff are third on three points with two games remaining.
A point against Sheriff will see United through to the knockout stage, but they need a win to stand any chance of winning their group and avoiding a two-leg playoff tie against one of the third-placed teams from the Champions League.
Meanwhile, Arsenal will go through as Group A winner if Mikel Arteta’s team avoid defeat against second-place PSV Eindhoven on Thursday.