Torino full-back Cristian Molinaro has torn a ligament in his left knee and will require surgery, depriving newly arrived goalkeeper Joe Hart of a key defender.
Molinaro injured his anterior cruciate ligament near the half-hour mark of Sunday's 0-0 draw with Empoli.
He could be out for up to six months.
Torino is already without leading forward Andrea Belotti, who injured his right thigh with Italy's national team earlier this month.
Belotti, who scored a hat trick against Bologna in August, is expected back in the next week or two.
England keeper Hart is on loan from Manchester City at Torino, who have four points from the opening four rounds.