The Frenchman is set to miss the busy Christmas period as he has a hamstring problem.
Fofana, whose load has been managed all season due to long term knee problems, came off during a 3-0 win over Aston Villa.
"Unfortunately it is bad news," coach Enzo Maresca said speaking after the match. "A hamstring problem. These kind of things usually require three, four, five weeks. In this moment, we lose him for 10 or 12 games. In the way he was playing, it's a big loss for us but we have more players and we can find a solution."
Asked if it was a big blow, he added: "It's a big loss, it's a big loss. He is doing fantastic but it is normal when you play this amount of games. Fortunately, it was his first injury of the season, but we will find a solution."
- Get breaking football news faster with the new Tribal Football app! Download now on iOS and Android to stay ahead of all the latest transfers and football updates. Download now: App Store, Google Play