Hugo Lloris and Moussa Sissoko have been ruled out of Sunday's trip to Watford.
Goalkeeper Hugo has a thigh problem while fellow France international Moussa has a hamstring injury, with both unavailable for this weekend's match.
Erik Lamela (hamstring) will be assessed ahead of Sunday's game. The attacking midfielder had been due to be among the substitutes for Monday's win at Manchester United but was injured in the warm-up and replaced by Luke Amos in a late change.
There is good news for midfielder Victor Wanyama, though, who is back in full training after suffering a knee injury in pre-season.
Young defender Juan Foyth, meanwhile, is in the late stages of rehab from a thigh injury.