Leaders Napoli again rely on Dries Mertens and Lorenzo Insigne, as Sassuolo try to cause another huge upset in the Scudetto race.
It kicks off at the Mapei Stadium in Reggio-Emilia at 19.45 GMT.
The Partenopei recovered from their upsets against Inter and Spartak Moscow by thrashing Lazio 4-0 at the weekend, consolidating their spot at the top of the table and going three points clear of Milan.
Matteo Politano is back in the squad after recovering from COVID-19, but Victor Osimhen and Andre Frank Zambo Anguissa are long-term absentees.
Mertens bagged a brace against Lazio and again leads the attack with support from Insigne, Piotr Zielinski and Hirving Lozano.
Sassuolo have been real giant-killers so far this season, earning victories away to both Juventus and Milan, conquering San Siro at the weekend to blow the title race wide open.
They could now return the favour by stalling Napoli, but Jeremie Boga, Filip Djuricic, Pedro Obiang and Filippo Romagna are still carrying knocks.
Gianluca Scamacca is chosen to lead the trident with Domenico Berardi and Giacomo Raspadori, but Hamed Junior Traore returns in midfield.
Sassuolo: Consigli; Toljan, Chiriches, Ferrari, Rogerio; Frattesi, Maxime Lopez, Traore; Berardi, Scamacca, Raspadori
Napoli: Ospina; Di Lorenzo, Rrahmani, Koulibaly, Mario Rui; Fabian Ruiz, Lobotka, Zielinski; Lozano, Mertens, Insigne