Goalkeeper Mandanda will miss four to six weeks with a torn right thigh muscle while Rami, a central defender, will be out for 10-15 days with a calf injury, the club said on Monday.
Both players came off injured as Marseille beat Dijon 3-1 in Ligue 1 on Saturday to maintain third spot.
Another central defender, Rolando, is also a doubt after finishing the Dijon game with an Achilles problem.
Marseille’s top scorer, France forward Florian Thauvin, who damaged a hamstring last week while on international duty, is also unlikely to play according to reports in local media.
Against RB Leipzig, Mandanda will be replaced by his usual understudy Yohann Pele, who came on against Dijon. On Saturday, Gregory Sertic replaced Rami for the last 10 minutes.
