Napoli start Faouzi Ghoulam, Lorenzo Insigne and Dries Mertens, while Alex Meret is in goal against his former SPAL teammates.
It kicks off at the Stadio San Paolo at 14.00 GMT.
The Partenopei sit in second place and hope to take advantage of a potential Juventus slip-up against Roma this evening.
Napoli start Faouzi Ghoulam, Lorenzo Insigne and Dries Mertens, while Alex Meret is in goal against his former SPAL teammates.
It kicks off at the Stadio San Paolo at 14.00 GMT.
The Partenopei sit in second place and hope to take advantage of a potential Juventus slip-up against Roma this evening.
Carlo Ancelotti enacts more squad rotation with an eye towards the Boxing Day showdown with third-placed Inter.
Kalidou Koulibaly and Insigne are one yellow card away from suspension, but are not rested despite the possibility they could miss the Inter clash.
Meret returns to the starting XI as he faces his former teammates at SPAL, where he had 13 Serie A appearances last season on loan from Udinese.
Ghoulam continues his return to full fitness after over a year out with knee injuries, while Marko Rog and Piotr Zielinski also get chances.
Allan is rested after suffering from a shoulder problem.
SPAL have several players who are not 100 per cent fit, including Simone Missiroli and Manuel Lazzari, while Thiago Cionek is back from suspension.
Alberto Paloschi is picked as partner to Mirco Antenucci rather than Andrea Petagna.
Leonardo Semplici’s side are winless in seven rounds, drawing four and losing three.
Napoli have won each of their last nine Serie A meetings with SPAL and are unbeaten against them in the top flight since March 1961.
Napoli: Meret; Hysaj, Albiol, Koulibaly, Ghoulam; Callejon, Rog, Hamsik, Zielinski; Insigne, Mertens
SPAL: Gomis; Cionek, Djourou, Bonifazi; Lazzari, Schiattarella, Valdifiori, Kurtic, Fares; Paloschi, Antenucci
Ref: La Penna