Napoli star Billy Gilmour and Scott McTominay behind Romelu Lukaku and Khvicha Kvaratskhelia for the tricky trip to Empoli.
It kicks off at the Stadio Castellani at 11.30 UK time (10.30 GMT).
The Partenopei are top of the table despite losing the opening match, winning five of their last six Serie A fixtures.
Stanislav Lobotka picked up a thigh injury on international duty and Alex Meret is still out of action, so Gilmour gets his first start with fellow Scotland star McTominay in midfield, supporting Lukaku, Kvaratskhelia and Matteo Politano.
This is the first match Napoli have played without Lobotka since April 2022.
Elia Caprile faces his former club and Leonardo Spinazzola steps in for not fully fit Mathias Olivera.
Empoli only suffered their first defeat of the season in a 2-1 loss to Lazio, after two victories and four draws.
All three of their home fixtures have ended 0-0 this term against Monza, Juventus and Fiorentina.
Saba Sazonov, Samuele Perisan, Luca Belardinelli, Youssef Maleh, Szymon Zurkowski and Tyronne Ebuehi are injured, but Mattia Viti shakes off a knock to his back.
Empoli vs. Napoli line-ups
Empoli: Vasquez; Goglichidze, Ismajli, Viti; Gyasi, Anjorin, Grassi, Pezzella; Fazzini, Esposito; Colombo
Napoli: Caprile; Di Lorenzo, Rrahmani, Buongiorno, Spinazzola; Anguissa, Gilmour, McTominay; Politano, Lukaku, Kvaratskhelia
Player statistic
| Alberto Grassi |  |
33' | ||
| 37' | |
Frank Anguissa |
| 63' |  |
Khvicha Kvaratskhelia | ||
| 76' | |
Giovanni Di Lorenzo |
Match statistic
