Victor Osimhen and Kvicha Kvaratskhelia spearhead the Napoli attack, as Carlo Ancelotti returns with Vinicius Junior and Jude Bellingham for Real Madrid.
It kicks off at the Stadio Diego Armando Maradona at 20.00 UK time (19.00 GMT).
The Partenopei had a shaky start to life under Rudi Garcia, not helped by Osimhen’s fury over the TikTok video mocking his penalty miss.
However, most of that seems to be behind them now after back-to-back victories over Udinese and Lecce with eight goals scored and one conceded.
Pierluigi Gollini, Amir Rrahmani and Juan Jesus are still out injured, so Natan makes his first Champions League start alongside Leo Ostigard in defence.
Kvaratskhelia also rediscovered his form, finding the net for the first time since March.
Real Madrid come to Naples without David Alaba, Arda Guler, Eder Militao and goalkeeper Thibaut Courtois.
Toni Kroos again gets the nod in midfield rather than Ballon d’Or winner Luka Modric, while Eduardo Camavinga is re-routed as a full-back.
Vinicius Junior was back in the starting XI against Girona at the weekend after a femoral bicep injury, but Bellingham is the form man with seven goals in eight games.
Rodrygo is picked to complete the attack rather than Joselu.
Ancelotti returns to the Stadio Maradona, where he was never particularly popular and sacked by President Aurelio De Laurentiis in December 2019.
The Merengues have won every game this season apart from a 3-1 derby defeat to Atletico Madrid.
Napoli: Meret; Di Lorenzo, Ostigard, Natan, Olivera; Anguissa, Lobotka, Zielinski; Politano, Osimhen, Kvaratskhelia
Napoli bench: Contini, Idasiak, Mario Rui, Elmas, Simeone, Zerbin, Cajuste, Lindstrom, D’Avino, Zanoli, Gaetano, Raspadori
Real Madrid: Kepa; Carvajal, Rudiger, Nacho, Camavinga; Valverde, Tchouameni, Kroos; Bellingham; Rodrygo, Vinicius
Real Madrid bench: Lunin, Canizares, Modric, Joselu, Lucas Vazquez, Dani Ceballos, Fran Garcia, Brahim Diaz, F Mendy, Carrillo
Ref: Turpin (FRA)
Player statistic
Leo Östigard | 19' | |||
27' | Vinícius Júnior (Assist: Jude Bellingham) | |||
29' | Eduardo Camavinga | |||
34' | Jude Bellingham (Assist: Eduardo Camavinga) | |||
Natan | 45' |
Piotr Zielinski | 54' | |||
70' | Jude Bellingham | |||
78' | Alex Meret | |||
89' | Kepa Arrizabalaga |