Napoli have Victor Osimhen back to lead the way with Lorenzo Insigne, but Fiorentina are missing Lucas Torreira and look to Arthur Cabral.
It kicks off at the Stadio Diego Armando Maradona at 14.00 UK time (13.00 GMT).
The pressure is back on the Partenopei, who are just one point off leaders Milan, but also have Inter breathing down their necks.
Osimhen returns from suspension to lead the attack, but Amir Rrahmani starts despite suffering from flu symptoms.
Andre-Frank Zambo Anguissa sits out a ban with Giovanni Di Lorenzo, Andrea Petagna, Kevin Malcuit and Adam Ounas injured.
Fiorentina have on-form Torreira suspended, while Giacomo Bonaventura and Alvaro Odriozola are on the treatment table, so the midfield is completely revamped.
Arthur Cabral gets the nod rather than Krzysztof Piatek upfront with Nico Gonzalez and Riccardo Saponara.
Napoli: Ospina; Zanoli, Rrahmani, Koulibaly, Mario Rui; Fabian Ruiz, Lobotka, Zielinski; Politano, Osimhen, Insigne
Fiorentina: Terracciano; Venuti, Milenkovic, Igor, Biraghi; Castrovilli, Amrabat, Duncan; Gonzalez, Cabral, Saponara