Gonzalo Higuain, Lorenzo Insigne and Dries Mertens start as Napoli need to beat Porto to continue in the Europa League.
It kicks off at 20.05 GMT at a packed out Stadio San Paolo, as fans have been flocking around the arena and causing traffic gridlock from a good four hours before kick-off.
Porto won the first leg 1-0, so Rafa Benitez’s men have to win by two clear goals to reach the Europa League quarter-finals.
Christian Maggio returned from Portugal last week with a chest injury that on the flight back developed into a collapsed lung.
He underwent emergency surgery and is expected to be out of action for around a month.
Also absent are goalkeeper Rafael Cabral and Juan Camilo Zuniga.
Higuain again leads the attack with support from Goran Pandev, Lorenzo Insigne and Dries Mertens, as Marek Hamsik and Jose Callejon are rested.
Henrique takes over at right-back from Maggio and Anthony Reveillere.
Porto are forced to make several changes, as goalkeeper Helton is ruled out for the rest of the season with an Achilles tendon injury on Sunday.
There is also a ban for key defender Alex Sandro, so Diego Reyes and Ricardo step in.
Ricardo Quaresma completes the trident attack with Jackson Martinez, who scored in the first leg, and Silvestre Varela.
Napoli: Reina; Henrique, Fernandez, Albiol, Ghoulam; Inler, Behrami; Mertens, Pandev, Insigne; Higuain
Napoli bench: Colombo, Reveillere, Britos, Callejon, Hamsik, Dzemaili, Duvan Zapata
Porto: Fabiano; Danilo, Mangala, Reyes, Ricardo; Carlos Eduardo, Fernando, Defour; Varela, Martinez, Quaresma
Porto bench: Kadu, Josue, Herrera, Lica, Agu, Quintero, Ghilas