Los Blancos, who are already through to the round of 16, sit top of the section on 10 points, four points ahead of second-placed Leipzig, who are bidding to join the reigning champions in the next round.
Match preview
Leipzig have won two and lost two of their four matches in the section to collect six points, which has left them second in the table, one point ahead of third-placed Shakhtar Donetsk ahead of the next set of games.
Shakhtar go to Celtic on Tuesday, with the Ukrainian outfit looking for their second victory in the section, but Leipzig would secure their spot in the next round of the competition if they manage to beat Real Madrid and Shakhtar lose in Scotland.
Marco Rose's side opened their Group F campaign with back-to-back defeats to Shakhtar and Real Madrid, which placed them in a very difficult position in terms of reaching the next round, but they have responded with back-to-back wins over Celtic to move onto six points.
Leipzig will welcome Real Madrid and then head to Shakhtar in their final two group games, and they will be determined to navigate their way into the next round of the competition.
The German outfit are actually unbeaten in their last seven matches in all competitions, which includes a 3-3 draw with Augsburg in the Bundesliga on Saturday, which has left them down in eighth position in the table.
Real Madrid, meanwhile, are already through to the next round of the competition, picking up 10 points from their opening four matches courtesy of a record of three wins and one defeat.
Carlo Ancelotti's side beat Celtic, Leipzig and Shakhtar in their opening three games in the section but needed a last-gasp equaliser from Antonio Rudiger to claim a point against Shakhtar in the away match last time out, with the 1-1 draw enough to take them into the round of 16 once again.
The holders, as mentioned, would be confirmed as group winners if they avoid defeat in this game, but they would have another chance to secure top spot against Celtic at Bernabeu on November 2 even if Leipzig manage to pull off a famous victory in front of their own supporters.
Real Madrid are still unbeaten in all competitions this season, and Saturday's 3-1 win over Sevilla in La Liga saw them once again open up a six-point advantage over second-placed Barcelona in the table.
Ancelotti's team have another five games before the campaign breaks for the 2022 World Cup, taking on Leipzig and Celtic in the Champions League, in addition to Girona, Rayo Vallecano and Cadiz in the league.
RB Leipzig Champions League form:
L
L
W
W
RB Leipzig form (all competitions):
W
D
W
W
W
D
Real Madrid Champions League form:
W
W
W
D
Real Madrid form (all competitions):
W
W
D
W
W
W
Team News
Leipzig will again be missing Lukas Klostermann, Marcel Halstenberg, Konrad Laimer and Peter Gulacsi on Tuesday evening through injury, while Timo Werner will need a late fitness test.
Rose's side were actually 3-0 down against Augsburg on Saturday before scoring three times in the final 20 minutes, and two of the goalscorers, Andre Silva and Christopher Nkunku, are certain starters here.
Amadou Haidara will also come back into the midfield on Tuesday night, but Yussuf Poulsen, Dani Olmo and Emil Forsberg could all miss out on starts in the final third of the field.
As for Real Madrid, Ancelotti has confirmed that Karim Benzema will not be available for this match, with the Frenchman absent against Sevilla due to muscular fatigue.
Dani Ceballos and Mariano Diaz are also set to miss out once again, but Thibaut Courtois made his return from injury against Sevilla and will again start between the sticks.
Ancelotti's desire to secure first spot in the section should mean that a strong XI is named here, although there could be a change from Saturday's side, with Rudiger potentially replacing Ferland Mendy.
Eden Hazard is an option through the middle in Benzema's absence, but it seems more likely that Federico Valverde, Rodrygo and Vinicius Junior will continue as the starting front three.
Valverde, though, will need to pass a late fitness test after picking up an issue against Sevilla.
RB Leipzig possible starting lineup:
Blaswich; Simakan, Orban, Gvardiol, Raum; Haidara, Schlager; Szoboszlai, Nkunku, Werner; A Silva
Real Madrid possible starting lineup:
Courtois; Carvajal, Militao, Rudiger, Alaba; Modric, Tchouameni, Kroos; Valverde, Rodrygo, Vinicius
We say: RB Leipzig 1-1 Real Madrid
Leipzig are in strong form at the moment and certainly have the tools to harm the reigning Spanish and European champions in this match. It is so difficult to back Real Madrid not to win at the moment, but this is a tough game for Ancelotti's side, and we can see the points being shared in a 1-1 draw.