Michel Bastos will require surgery, but Lyon hope the full-back will return before the end of the season.
The 27-year-old defender has suffered an injury to his left knee and will be forced to go under the knife in order to repair the damage.
Scans on Monday revealed the full extent of the problem and it has been decided that an operation is now the only option.
Bastos is due to fly back to his native Brazil over the weekend, where he will undergo medical treatment.
Edilson Thiele, one of the surgeons for the Brazilian national team, will carry out the procedure.
Lyon, who crashed out of the UEFA Champions League to Real Madrid on Wednesday, are disappointed to see a key man sidelined but are confident Bastos will play again this term.
Coach Claude Puel said: "It is an inconvenience.
"I am not a surgeon but we hope we can have him available towards the end of the season."