N'Golo Kante lasted just a dozen minutes of Chelsea's crucial Premier League clash with Manchester United before coming off with an injury to his right leg.
The France midfielder hobbled off after some medical treatment but was judged unable to continue after Frank Lampard's team had made a bright start at Stamford Bridge.
Kante's campaign has been ruined by a series of injuries to his hamstring and ankle.
It is another significant blow for an already injury-depleted team at the start of an eight day stretch that also sees Chelsea welcome Jose Mourinho's Tottenham Hotspur to West London in another Premier League test on Saturday lunchtime before hosting Bayern Munich in the first leg of their Champions League round of 16 tie.
Tammy Abraham and Callum Hudson-Odoi both missed the United game with ankle and hamstring injuries respectively.
The former has been struggling for three weeks with his issue and failed a fitness test on Monday having failed to take a full part in training last week.
The extent of Hudson-Odoi's injury is not yet clear, although it is understood not to be too severe.
Christian Pulisic remains sidelined with an unspecified issue after Lampard confirmed last week that he had suffered a setback, while Ruben Loftus-Cheek is not yet fit following his long-term achilles issue.
Mason Mount replaced Kante, though the Blues needed to play with 10 men for two minutes as the England player was not prepared to come on.
