Napoli have Victor Osimhen back on the bench, but Giacomo Raspadori and Kvicha Kvaratskhelia again lead the attack against Ajax after a 6-1 victory in Amsterdam.
It kicks off at the Stadio Diego Armando Maradona at 17.45 UK time (16.45 GMT).
The Partenopei have won their last eight games in all competitions, topping this Champions League group and the Serie A table, so just a point here would be enough to book their place in the Round of 16.
Amir Rrahmani is injured following a muscular strain, but Osimhen is back on the bench after a long lay-off, so Juan Jesus steps into defence.
Hirving Lozano is chosen rather than Matteo Politano in the trident attack with Raspadori and Kvaratskhelia.
Ajax were humiliated 6-1 on home turf last week, an historic result, and captain Dusan Tadic is suspended after his dismissal.
Devyne Rensch and Mohammed Ihattaren are out of action, but Steven Berghuis steps in with Steven Bergwijn and on-form Mohammed Kudus.
Napoli: Meret; Di Lorenzo, Kim, Juan Jesus, Olivera; Anguissa, Lobotka, Zielinski; Lozano, Raspadori, Kvaratskhelia
Ajax: Pasveer; Sanchez, J Timber, Bassey, Blind; Taylor, Alvarez, Klaassen; Berghuis, Kudus, Bergwijn