Chris Smalling and Lorenzo Pellegrini are out of the Roma squad to face Empoli on Sunday, but Jose Mourinho confirmed Paulo Dybala and Romelu Lukaku will start together.
It kicks off at the Stadio Olimpico on Sunday at 19.45 UK time (18.45 GMT).
The coach had warned in his press conference that Smalling and Pellegrini were not in good shape, the midfielder sent home early from international duty with Italy due to a muscular issue.
They have both been left out of the squad completely, so are not even going to be on the bench tomorrow evening.
Gianluca Mancini was also sent back early from the Azzurri camp, but is expected to play, partnered by debutant Evan N’Dicka in defence.
Mourinho said today that Lukaku and Dybala will start together for the first time.
Tammy Abraham and Marash Kumbulla are long-term absentees after tearing their anterior cruciate ligaments last season.
Roma squad for Empoli: Rui Patricio, Boer, Svilar, Karsdorp, Ndicka, Llorente, Celik, Mancini, Spinazzola, Cristante, Paredes, Sanches, Aouar, Kristensen, Bove, Zalewski, Pagano, Pisilli, Belotti, Azmoun, Dybala, Lukaku, El Shaarawy