Inter have the chance to go four points clear at the top with Marcus Thuram and Lautaro Martinez, but Lazio look to Ciro Immobile, Daichi Kamada and Matteo Guendouzi.
It kicks off at the Stadio Olimpico at 19.45 GMT.
Juventus were held to a 1-1 draw by Genoa on Friday, so this is a huge opportunity for the Nerazzurri to break clear, but Simone Inzaghi must first get past his former club.
Alexis Sanchez, Denzel Dumfries, Benjamin Pavard, Stefan de Vrij and Juan Cuadrado are out of action, so Yann Bisseck gets the nod on the right wing, moving Matteo Darmian into the back three.
Lazio have Patric only fit for the bench, while Alessio Romagnoli and Gustav Isaksen are injured.
Luis Alberto is surprisingly benched in favour of Daichi Kamada, behind Felipe Anderson, Immobile and Mattia Zaccagni.
This is traditionally a tough fixture for Inter, who have managed just one point from their last four trips to the Olimpico, without a win since October 2018.
Former Lazio and Inter player Sinisa Mihajlovic died a year ago this week, so his brother is at the Stadio Olimpico for this anniversary.
Lazio: Provedel; Lazzari, Casale, Gila, Marusic; Guendouzi, Rovella, Kamada; Felipe Anderson, Immobile, Zaccagni
Inter: Sommer; Bisseck, Acerbi, Bastoni; Darmian, Barella, Calhanoglu, Mkhitaryan, Dimarco; Thuram, Lautaro Martinez
Player statistic
| 26' |  |
Marcus Thuram | ||
| 40' |  |
Lautaro Martínez |
| 61' | |
Nicolò Barella | ||
| 66' | |
Marcus Thuram (Assist: Nicolò Barella) | ||
| Nicolò Casale | |
81' | ||
| Manuel Lazzari |  |
86' |
Match statistic
