Kroos is absent due to a hip complaint, while Ferland Mendy, Dani Carvajal and Alvaro Odriozola will also miss out, which has left head coach Carlo Ancelotti with a lack of options at the back.
David Alaba will make his debut in the middle of the defence, and the Austrian could be joined by Nacho, with Lucas Vazquez set to feature at right-back due to the absences of Carvajal and Odriozola.
Federico Valverde could benefit from Kroos's issue to feature alongside Casemiro and Luka Modric in midfield, while Ancelotti also has problems in the final third of the field.
Karim Benzema is back training with Real Madrid after a spell out with coronavirus, but the France international is unlikely to start and could therefore be named among the substitutes.
Eden Hazard, meanwhile, is battling back from a hamstring problem, and the Belgium international might not be risked from the start, which could open the door for Rodrygo and Luka Jovic to feature alongside Vinicius Junior in the final third of the field.
Ancelotti also has the option of playing a false nine, with Isco the most likely candidate, but Jovic could be given the chance to make his mark from the first whistle.
Real Madrid possible starting lineup: Courtois; Vazquez, Nacho, Alaba, Marcelo; Modric, Casemiro, Valverde; Rodrygo, Jovic, Vinicius