Madrid are currently in disarray across the back line, with Marcelo, Alvaro Arbeloa and Fabio Coentrao all sidelined.
As a result, coach Jose Mourinho took on Celta Vigo at the weekend with midfielder Michael Essien at left-back, centre-half Sergio Ramos at right-back and rookie Raphael Varane in the middle.
Such a situation is far from ideal in arguably the tightest of the eight groups, with Madrid (six points), Dortmund (four) and Manchester City (one) all desperate to get through and top spot in Group D still up for grabs.
The return of defensive midfielder Sami Khedira should help Madrid's cause in Germany, but he accepts it will be no easy night.
"I think that Dortmund are a great team, but so are Manchester City," he said, first assessing the state of the group.
"I believe that all three teams - and also Ajax - are great teams, so we cannot afford to focus only on Borussia.
"But, if we win, it's clear we will have taken a big step towards classification as first in the group.
"Dortmund are a compact team, they play in a block and also at great pace for 90 minutes. They are disciplined tactically, and have a lot of quality, especially in attack."
Dortmund will be taking to their home ground of Signal Iduna Park for the first time since the weekend's bad-tempered clash with Schalke.
Crowd violence marred the derby game but, according to former Stuttgart midfielder Khedira, it is an exciting place to play.
"It's a special time, because the atmosphere is always unique in Germany," he said.
"Playing at Dortmund is always nice, because it has a special atmosphere. The atmosphere of champions."
Dortmund were considered to be mightily unlucky not to take all three points from their last outing at Manchester City.
A brilliant display of goalkeeping by Joe Hart prevented them from adding to their goal, before a late, controversial penalty made it 1-1.
A league loss to Schalke is their most recent form, though, and manager Jurgen Klopp said: "We did not play well against Schalke, but there is nothing we can do to change that.
"The match against Real Madrid remains a cool match."
Key midfielder Jakub Blaszczykowski will be missing again for Dortmund, but left-back Marcel Schmelzer, midfielder Ilkay Guendogan and playmaker Mario Goetze are set to return.