Lazio look to Ciro Immobile, Luis Alberto and Sergej Milinkovic-Savic as they try to shake off the Rome Derby disappointment, but giant-killers Sassuolo have Gianluca Scamacca and Giacomo Raspadori.
It kicks off at the Stadio Olimpico at 17.00 UK time (16.00 GMT).
Serie A Liveblog: Spezia-Venezia, Lazio-Sassuolo, Salernitana-Torino
Maurizio Sarri’s men saw their hopes of a European spot and their overall confidence hit hard by a 3-0 defeat to arch-rivals Roma, which pushed them down to seventh place.
Sassuolo are only six points behind them and could close the gap with a victory here, having already won away to Juventus, Milan and Inter this season.
Pedro is suspended and Stefan Radu injured, so Manuel Lazzari completes the trident attack with Immobile and Felipe Anderson.
There are question marks over the future of Milinkovic-Savic and Luis Alberto, while Patric comes into the defence.
Sassuolo have Raspadori back from his ban, fresh from scoring two goals for Italy against Turkey, but Domenico Berardi and Maxime Lopez are carrying injuries.
Lazio: Strakosha; Lazzari, Patric, Acerbi, Marusic; Milinkovic-Savic, Leiva, Luis Alberto; Felipe Anderson, Immobile, Zaccagni
Sassuolo: Consigli; Muldur, Chiriches, Ferrari, Kyriakopoulos; Frattesi, Henrique; Defrel, Raspadori, Traore; Scamacca