Kostas Manolas is back in the Napoli XI against his former teammates, but Roma switch to a three-man defence in this head-to-head for fifth place.
The Derby del Sole kicks off at 20.45 UK time (19.45 GMT).
This is a straight showdown for fifth place, as both are now seemingly too far off Atalanta and the Champions League spots following midweek defeats.
Napoli lost 2-0 to Atalanta, with David Ospina picking up a head injury and therefore absent this evening, along with Allan, Fernando Llorente and Kevin Malcuit.
Arkadiusz Milik gets the nod with Lorenzo Insigne and Jose Callejon, resting Dries Mertens, but the big news is the first Manolas start since the lockdown and he does it against his former teammates.
Roma were embarrassed 2-0 at home by Udinese to further intensify their current crisis, as it was their second consecutive defeat.
Diego Perotti is suspended after his red card, with Juan Jesus injured, but Nicolò Zaniolo returns to the bench for the first time since knee surgery in January.
Edin Dzeko leads the attack with support from Henrikh Mkhitaryan and Justin Kluivert.
The big news is the change of system, as Paulo Fonseca has been testing a three-man defence in training and unleashes it here, with Roger Ibanez, Gianluca Mancini and Chris Smalling.
Pau Lopez also returns in goal after suffering a micro-fracture in his wrist during the lockdown.
Napoli: Meret; Di Lorenzo, Manolas, Koulibaly, Mario Rui; Fabian Ruiz, Demme, Zielinski; Callejon, Milik, Insigne
Roma: Pau Lopez; Ibanez, Mancini, Smalling; Zappacosta, Pellegrini, Veretout, Spinazzola; Mkhitaryan, Kluivert; Dzeko
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