The France defender has undergone hamstring surgery and Chelsea have confirmed Fofana won't play again this season.
Fofana had only returned in March after three months out with a similar problem.
He has now undergone surgery, which was performed on Saturday, and his recovery will take him into the offseason.
"The club can confirm that defender Wesley Fofana has today undergone successful hamstring surgery," a Chelsea statement said.
"Wesley was assessed by specialists this week after the 24-year-old suffered an injury of the muscle. Following that assessment, it was concluded that an operation would be required.
"The 24-year-old will now begin his recovery and undergo rehabilitation with the club's medical staff at Cobham over the coming weeks."