Napoli are forced into a complete revamp amid an injury crisis for this tricky trip to a SPAL side in the mood for celebration.
It kicks off at the Stadio Paolo Mazza at 17.00 UK time (16.00 GMT).
Carlo Ancelotti must do without injured Dries Mertens, Lorenzo Insigne, Adam Ounas, Nikola Maksimovic and Vlad Chiriches, while David Ospina is on family leave in Colombia.
Amin Younes has been impressing over the last few weeks and he starts on the left, while Piotr Zielinski is given a new more advanced role alongside Arkadiusz Milik.
Sebastiano Luperto and Kevin Malcuit get rare starts.
Jasmin Kurtic has failed a fitness test, while Andrea Petagna is partnered by Sergio Floccari.
SPAL are in the mood to celebrate, having secured their Serie A safety with three rounds to spare.
SPAL: Viviano; Bonifazi, Vicari, Cionek; Lazzari, Missiroli, Murgia, Valoti, Fares; Petagna, Floccari
Napoli: Meret; Malcuit, Luperto, Koulibaly, Mario Rui; Callejon, Allan, Fabian Ruiz, Younes; Zielinski, Milik