Inter and Roma both try to get back on track in the Scudetto race, but Romelu Lukaku and Marcelo Brozovic are out, while Jose Mourinho unveils a new approach with Paulo Dybala as centre-forward.
It kicks off at San Siro at 17.00 UK time (16.00 GMT).
This represents a return to the Stadio Meazza for Treble-winner Mourinho, but he is in the stands due to a touchline ban for protesting refereeing decisions.
Simone Inzaghi is trying to hang on to his job after a series of poor results this season, not helped by injuries to Lukaku and Brozovic.
At least he had time to prepare, because the Croatian would’ve been suspended anyway, so Kristjan Asllani starts in midfield and Hakan Calhanoglu is back.
Edin Dzeko partners Lautaro Martinez, with an eye also on the upcoming Champions League showdown with Barcelona.
Francesco Acerbi is again chosen in place of Stefan de Vrij.
Roma are still missing Rick Karsdorp, Georginio Wijnaldum and Ebrima Darboe.
The good news is Dybala and Pellegrini have shaken off their muscular issues and can start with Nicolo’ Zaniolo, but Tammy Abraham is dropped, using La Joya as a centre-forward.
Both sides went into the break for international duty off defeats, as Inter fell 3-1 away to Udinese and Roma lost at home to Atalanta.
The Giallorossi have not beaten Inter in any competition, home or away, since a 3-1 result at San Siro in February 2017, followed by six draws and five defeats, losing their last four in a row between Serie A and the Coppa Italia.
Inter: Handanovic; Skriniar, Acerbi, Bastoni; Dumfries, Barella, Asllani, Calhanoglu, Dimarco; Dzeko, Lautaro Martinez
Roma: Rui Patricio; Mancini, Smalling, Ibanez; Celik, Cristante, Matic, Spinazzola; Pellegrini, Zaniolo; Dybala