Sassuolo will face Napoli without forwards Francesco Caputo, Domenico Berardi or Filip Djuricic.
It kicks off on Sunday at 17.00 GMT, click here for a match preview.
Coach Roberto De Zerbi is still unbeaten so far this season, but has to radically revamp his squad at the Stadio San Paolo.
Hitman Caputo scored five goals in five Serie A games, but he is ruled out with a muscular problem sustained in training this morning.
Berardi and Djuricic are also out of action, with Lukas Haraslin, Jeremy Toljan, Nicolas Schiappacasse and Filippo Romagna on the treatment table.
Italy Under-21 international Giacomo Raspadori could therefore start with Jeremie Boga and Gregoire Defrel.
Sassuolo squad for Napoli: Consigli, Pegolo, Turati, Vitale; Ayhan, Chiriches, Ferrari, Kyriakopoulos, Marlon, Muldur, Peluso, Piccinini, Rogerio; Bourabia, Locatelli, Lopez, Obiang, Steau, Traorè; Boga, Defrel, Raspadori