Souleymane Diawara's season could be over after tests revealed that the Marseille centre-back tore the anterior cruciate ligament in his right knee in the 1-1 draw at Nice on Saturday.
The Senegalese international defender was forced off after just six minutes at Stade du Ray and left the ground on crutches.
Marseille said that tests conducted by the club's medical staff on Sunday morning "revealed signs of a serious knee sprain with torn anterior cruciate ligaments".
Charles Kabore replaced Diawara at Nice, only to be sent off shortly before half-time following a high foul on Elliot Grandin.
Diawara was already suspended for the first leg of Marseille's Champions League quarter-final at home to Bayern Munich on Wednesday, along with goalkeeper and captain Steve Mandanda.
Marseille's draw at Nice ended a club-record run of seven defeats in all competitions but left them 13 points off the pace in the battle for Champions League qualification.
They will face Lyon in the French League Cup final on April 14.