The Blues star had almost completely recovered from the calf strain he sustained against Watford in the Premier League at the beginning of May, but he has now encountered another serious set-back in his road to recovery.
He had been taking part in preparations ahead of the Europa League decider against Arsenal when he suffered a twisted knee and his involvement in the game remains doubtful as a result.
Maurizio Sarri had indicated last week that he was optimistic the France international could play a part in the game against the Gunners, so the injury comes as a blow and he will now have to consider alternative arrangements.
Indeed, Kante is not the only concern for Sarri in the build up to the all-Premier League encounter in Baku, with Jorginho also sustaining a knock in last week's open training session.
The Chelsea boss is already without both Callum Hudson-Odoi and Ruben Loftus-Cheek who both suffered ruptured Achilles tendon injuries, with the latter having suffered his set-back in a post season friendly match against New England Revolution.
Antonio Rudiger, meanwhile, is out with a knee injury that needed surgery.
There is some good news, however, as Ethan Ampadu has returned from a back injury and the Wales international will likely make the bench for the final.
Chelsea's Europa League clash against Arsenal is set to be played at Baku's Olympic Stadium on Wednesday, May 29.
Sarri has already secured Champions League football for the Blues by guiding the club to a third-place finish in the Premier League, but he will be eager to land silverware as speculation swirls around his future.
"We lost two, three games very badly, but we finished third, we got to the League Cup final, a very difficult competition, and now we have the opportunity to play the Europa League final."
The Italian coach added: "I'm very happy to stay in the Premier League and Chelsea is one of the most important clubs in the Premier League."