Giovanni Simeone leads the Napoli attack with Kvicha Kvaratskhelia, as Victor Osimhen is only fit for the bench, while Real Madrid look to Brahim Diaz and Jude Bellingham.
It kicks off at the Bernabeu at 20.00 GMT.
Walter Mazzarri took over from Rudi Garcia during the break for international duty and made his debut with a surprise Serie A victory away to Atalanta.
Osimhen made his comeback in that game, albeit off the bench, and is still not fully fit after two months out with a thigh strain.
Simeone therefore gets the nod upfront with Kvaratskhelia and Matteo Politano.
Alex Meret returns in goal after a calf strain, but Juan Jesus is a makeshift left-back in the absence of both Mathias Olivera and Mario Rui, while Jesper Lindstrom is also injured.
Carlo Ancelotti and Real Madrid have already secured their spot in the Round of 16 and are sure of the leadership, so can relax and enjoy this evening.
Rodrygo and former Milan man Brahim Diaz return after injury and illness, while top scorer Bellingham is fully recovered from a dislocated shoulder.
However, there are numerous absentees, including Thibaut Courtois, Vinicius Junior, Luka Modric, Eduardo Camavinga, Arda Guler, Kepa Arrizabalaga, Eder Militao and Aurelien Tchouameni.
Theo Zidane, son of ex-coach Zinedine, is on the bench and awaiting his debut.
Napoli can qualify for the Round of 16 tonight if they win here, or draw and SC Braga fail to beat Union Berlin.
They can even afford to lose as long as Braga are defeated by the Germans.
Real Madrid: Lunin; Carvajal, Rudiger, Alaba, Mendy; Valverde, Kroos, Ceballos; Bellingham; Brahim Diaz, Rodrygo
Real Madrid bench: Fran Gonzalez, Canizares, Nacho, Joselu, Lucas Vazquez, Fran Garcia, Mario Martin, Nico Paz, Gonzalo, Theo Zidane
Napoli: Meret; Di Lorenzo, Rrahmani, Natan, Juan Jesus; Anguissa, Lobotka, Zielinski; Politano, Simeone, Kvaratskhelia
Napoli bench: Contini, Gollini, Elmas, Osimhen, Zerbin, Cajuste, Ostigard, Zanoli, Gaetano, Raspadori
Ref: Letexier (FRA)
Player statistic
| 10' |  |
Giovanni Simeone (Assist: Giovanni Di Lorenzo) | ||
| Rodrygo (Assist: Brahim Díaz) |
|
11' | ||
| Jude Bellingham (Assist: David Alaba) |
|
22' |
| 47' | |
Frank Anguissa | ||
| 49' |  |
Piotr Zielinski | ||
| Nico Paz (Assist: Antonio Rüdiger) |
|
84' | ||
| Joselu (Assist: Jude Bellingham) |
|
90+4' | ||
| 90' | |
Jens Cajuste |
Match statistic
