Lazio have a full-strength starting XI with Luis Alberto and Joaquin Correa joining Ciro Immobile, but Roma are decimated by injuries.
It kicks off at the Stadio Olimpico at 17.00 GMT.
This is a fascinating Derby della Capitale between Roma in fourth and Lazio third, although the Biancocelesti actually have a game in hand, so could even be ahead of Inter.
Simone Inzaghi has taken the Aquile to new heights with 11 consecutive Serie A victories, to go along with their Coppa Italia and Italian Super Cup trophies.
There was a blow to their confidence midweek with a surprise 1-0 defeat to Napoli, which knocked them out of the Coppa Italia quarter-finals.
Luis Alberto and Correa missed that game through injury, but both are back for this massive fixture, as they could go into second place after Inter’s 1-1 draw with Cagliari.
They support Immobile, who is Capocannoniere on an incredible 23 Serie A goals in 19 games, not to mention front-runner for the Golden Shoe award as Europe’s most prolific player.
Danilo Cataldi, Jordan Lukaku and Adam Marusic are the only remaining absentees.
Roma wish they could say that, because once again coach Paulo Fonseca has choices forced upon him by a spate of injuries.
Diego Perotti and Javier Pastore are back in the squad, but by no means fit to start, whereas Nicolò Zaniolo, Henrikh Mkhitaryan, Amadou Diawara, Davide Zappacosta and Mirco Antonucci are out of action.
Bryan Cristante therefore partners Jordan Veretout in midfield, with Cengiz Under, Lorenzo Pellegrini and Justin Kluivert supporting Edin Dzeko.
The surprises are at full-back, where Davide Santon and Leonardo Spinazzola are preferred to Alessandro Florenzi and Aleksandar Kolarov.
The Giallorossi also went out of the Coppa with a heavy midweek defeat to Juventus.
The result back in September was 1-1, but Lazio have not gone unbeaten in both Serie A derbies since the 2012-13 season, when Vladimir Petkovic was in charge.
Expect fireworks, as this clash has seen 24 red cards since 2000, at least two mor than any other fixture in Europe’s top five leagues.
Roma: Pau Lopez; Santon, Mancini, Smalling, Spinazzola; Cristante, Veretout; Under, Pellegrini, Kluivert; Dzeko
Lazio: Strakosha; Luiz Felipe, Acerbi, Radu; Lazzari, Milinkovic-Savic, Leiva, Luis Alberto, Lulic; Correa; Immobile
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