The Champions of Italy make their home debut with Victor Osimhen, though Kvicha Kvaratskhelia is on the bench, but Sassuolo are still without Domenico Berardi.
It kicks off at the Stadio Diego Armando Maradona at 19.45 UK time (18.45 GMT).
The Partenopei began the defence of their title with a 3-1 comeback win away to Frosinone, so this is the home debut for new coach Rudi Garcia.
Kvaratskhelia missed that trip with a muscular issue, but he is back on the bench, so Osimhen is supported by Matteo Politano and Giacomo Raspadori.
Sassuolo lost at home to Atalanta and are again without captain Berardi, who is trying to force through a transfer to Juventus.
Gregoire Defrel and Filippo Missori are not 100 per cent fit, with Agustin Alvarez a long-term absentee, but Ruan Tressoldi returns from suspension.
In their last three games against Napoli, Sassuolo scored one goal and conceded 12.
Napoli: Meret; Di Lorenzo, Rrahmani, Juan Jesus, Olivera; Anguissa, Lobotka, Zielinski; Politano, Osimhen, Raspadori
Sassuolo: Consigli; Toljan, Erlic, Ruan Tressoldi, Vina; Boloca, Lopez, Matheus Henrique; Bajrami, Pinamonti, Laurienté
Player statistic
| Victor Osimhen |  |
16' | ||
| 30' |  |
Ruan Tressoldi |
| 51' |  |
Maxime Lopez | ||
| Giacomo Raspadori |  |
60' | ||
| Giovanni Di Lorenzo (Assist: Khvicha Kvaratskhelia) |
 |
64' |
Match statistic
