Beaten with relative ease by Manchester City last year, Carlo Ancelotti is attempting to make more history in this competition.
A four-time winner of the Champions League himself, the Italian could extend his personal record to five but first must overcome Leipzig.
While the German side are underdogs, they have been strong at home in Europe for a while now and the fact Jude Bellingham is likely to miss the game should give them confidence.
Where to watch RB Leipzig vs Real Madrid
TV channel: The game will be broadcast on TNT Sports 2. Coverage starts at 7.30pm GMT ahead of an 8pm kick-off.
Live stream: Subscribers will be able to watch on a live stream via the Discovery+ App.
LIVE coverage: Follow all the action with Standard Sport’s dedicated match blog!