Atalanta hope to continue their free-scoring form with Ademola Lookman and Rasmus Hojlund, but Sassuolo are fresh from a shock 5-2 win over Milan with Domenico Berardi taking centre-stage.
It kicks off at the Mapei Stadium in Reggio Emilia at 19.45 GMT.
La Dea have really rediscovered their exciting spirit in 2023, amassing 11 points in the last five rounds, scoring 17 goals in the process, but were eliminated from the Coppa Italia with a 1-0 defeat to Inter on Tuesday.
Lookman is in great shape, while today is prodigious hitman Hojlund’s 20th birthday, but Jeremie Boga is benched against his former club.
Davide Zappacosta and Jose Luis Palomino are out injured.
Sassuolo had been in disastrous form with just two points from eight rounds until the shock 5-2 victory away to reigning champions Milan.
Berardi contributed a goal and three assists in that game and he leads the way again with Gregoire Defrel and Armand Laurienté.
The Neroverdi also throw new signings Nedim Bajrami and Nadir Zortea – from Empoli and Atalanta respectively – straight into the squad after deadline day transfers.
Mert Muldur, Andrea Pinamonti and Jeremy Toljan are injured.
Sassuolo: Consigli; Zortea, Erlic, Tressoldi, Rogerio; Frattesi, Obiang; Berardi, Matheus Henrique, Laurienté; Defrel
Atalanta: Musso; Toloi, Djimsiti, Scalvini; Hateboer, De Roon, Ederson, Maehle; Koopmeiners, Lookman; Hojlund