"Andre-Pierre Gignac has suffered a broken metatarsal. He will be sidelined for six weeks according to the medical staff," the club said on their website.
L'OM face Borussia Moenchengladbach in the Europa League on Thursday.
After two poor years at Marseille, injury-prone Gignac played a key role in his club's six league wins to start the season, during which he scored five goals.
Marseille were the first team to win their first six games since Monaco in the 1960-61 season. Monaco went on to be crowned champions at the end of that campaign.
Marseille, who took only one point from their last three league games, are second on 19 points from nine games, behind leaders Paris St Germain on goal difference.