Matias Vecino and Danilo Cataldi are out of Lazio’s trip to Milan on Saturday with a thigh injury, while Mattia Zaccagni is also a major doubt in this head-to-head for the top four.
It kicks off at San Siro on Saturday at 14.00 UK time (13.00 GMT).
The Biancocelesti consolidated second place with a 2-0 victory over Sassuolo, but lost Vecino to a thigh issue during the second half.
A statement from the club medical staff today confirmed that Vecino has been diagnosed with a small lesion to the femoral bicep in his right thigh and is therefore out of the match.
He had only started against Sassuolo as the replacement for injured Cataldi, who has a calf strain, so the options are limited in that role for coach Maurizio Sarri.
Toma Basic came off the bench and scored on Wednesday and is expected to step in with Marcos Antonio, so Luis Alberto could be pushed to the bench.
Another problem for Lazio is that Zaccagni missed the last two training sessions with a knock and is only likely to be fit for a place on the bench.
Instead, Pedro should step in to complete the trident with Ciro Immobile and Felipe Anderson.
Alessio Romagnoli returns from suspension in time to face his former club.