Roma start Andrea Belotti, who became a father this weekend, with Paulo Dybala and Nicolò Zaniolo, while Lecce give Samuel Umtiti his Serie A debut.
It kicks off at the Stadio Olimpico at 19.45 UK time (18.45 GMT).
Jose Mourinho is back on the bench after his ban for the win away to Inter, but is also still fuming after a midweek Europa League home defeat to Real Betis.
Tammy Abraham continues to be in poor form and is dropped in favour of Belotti, who became a father for the second time this weekend and is therefore in a mood to celebrate.
He is supported by Dybala and Zaniolo, with Lorenzo Pellegrini back in midfield, while Zeki Celik, Rick Karsdorp and Georginio Wijnaldum are injured.
Lecce won the Serie B title last season and have only lost three this term, drawing 1-1 four times including against Napoli.
Their only victory was 2-1 away to Salernitana, with Bistrovic the sole injury absentee.
Coach Marco Baroni finally unleashes Umtiti, on loan from Barcelona, for his Serie A debut.
Roma: Rui Patricio; Mancini, Smalling, Ibañez; Zalewski, Cristante, Pellegrini, Vina; Dybala, Zaniolo; Belotti
Lecce: Falcone; Gendrey, Baschirotto, Umtiti, Pezzella; Gonzalez, Hjulmand, Askildsen; Strefezza, Ceesay, Banda