Carlo Ancelotti will face his former club already safe in the knowledge that his Real team will be in the knockouts in the new year, with top spot all that is left to play for.
Match preview
Four wins from four in the group so far mean Real Madrid are huge favourites to progress as winners of the section, and they only need a point here to ensure they will be seeded for the last 16 draw in December.
That is something that is highly likely, considering Los Blancos have not lost at home since early April, and have won eight of their last nine Champions League home games, with a draw against Manchester City in last season's semi-final the outlier.
Real's recent record against Italian opposition has been formidable too, as they have won all of their last nine encounters against sides from Serie A, including a 3-2 win at the Maradona on matchday two.
A clean sheet is all Real need, and their defence on home soil has been fantastic this season, despite serious injuries to the likes of Thibaut Courtois and Eder Militao.
Hugo Duro's goal for Valencia late on when Real found themselves 5-0 up in their last league outing was the first goal they conceded here for almost 10-and-a-half hours.
One game during that run was a 3-0 success over Braga on matchday four, as that game saw them seal progression to the last 16, but stand-in keeper Andriy Lunin was forced into an early penalty save.
Ancelotti's side returned to action at the weekend with a comfortable 3-0 win over Cadiz which moved them to the top of La Liga, following Girona's failure to beat Athletic Bilbao on Monday.
Napoli will join Real in the last 16 if they win or simply match Braga's result against Union Berlin this week.
Union Berlin's woes this season means the Neapolitans are assured of some sort of European football in the new year, whether that be Champions League or Europa League, but their win in Braga means they remain huge favourites for second.
It will be a fifth consecutive progression past a UEFA group stage for Napoli, and they will hope it is a second successive one in this competition, where they reached the quarter-finals last season - a new club record.
This season has been much more tumultuous than the highs of last season under Luciano Spalletti though, as Rudi Garcia was sacked during the international break just four months into the season.
The Frenchman's departure came after a home defeat to Empoli, which itself came just days after being held by Union Berlin, a side who were on a 12-game losing run at the time.
Walter Mazzarri has returned to the club and will now prepare for a first ever meeting against Real Madrid in his managerial career.
Mazzarri's reign started with a fine 2-1 win away at Atalanta over the weekend, where Elif Elmas netted a late winner for the Partenopei.
That result extends their fine run of away form to seven wins in nine matches on the road this season, with draws against Genoa and Bologna the only minor blips, as they have also averaged over two goals per game in those nine outings.
Real Madrid Champions League form:
W
W
W
W
Real Madrid form (all competitions):
W
W
D
W
W
W
Napoli Champions League form:
W
L
W
D
Napoli form (all competitions):
W
D
W
D
L
W
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Team News
Ancelotti could decide to rotate and protect some of his Real Madrid players showing fitness problems ahead of this clash, knowing they only need a point.
Luka Modric is the most likely to be given the night off after he came off with a slight muscular problem over the weekend.
Jude Bellingham and Rodrygo both shrugged off injury problems to star for the side in the win at Cadiz on Sunday, and with injuries to other key players, they may both start again.
They include Vinicius Junior, who has been ruled out for the rest of 2023, and midfield pairing Aurelien Tchouameni and Eduardo Camavinga, who are also both unlikely to feature before the new year.
After his heroics on matchday four, Lunin may start again on goal, as Kepa Arrizabalaga is still a doubt and Courtois still has several months out.
Napoli are facing a crisis at left-back, as Mathias Olivera was stretchered off in the first half of their win at Atalanta, joining Mario Rui on the sidelines.
Juan Jesus is the likely player to come in given his versatility, while Amir Rrahmani and Natan are set to start in the centre.
Victor Osimhen made his long-awaited comeback after seven weeks out in the weekend win, coming off the bench shortly after the hour mark and assisting the winning goal, so he could replace Giacomo Raspadori in the starting XI.
Real Madrid possible starting lineup:
Lunin; Lucas Vazquez, Rudiger, Alaba, Nacho; Valverde, Kroos, Brahim Diaz, Bellingham; Joselu, Rodrygo
Napoli possible starting lineup:
Meret; Di Lorenzo, Rrahmani, Natan, Juan Jesus; Lobotka, Zambo Anguissa, Zielinski; Politano, Osimhen, Kvaratskhelia
We say: Real Madrid 2-1 Napoli
Real only need a draw to advance as group winners, and despite a large number of injury concerns, they should keep up their fine home record in this competition.
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