Courtois missed the weekend against Osasuna in La Liga with a back problem and did not train on Monday, suggesting Andriy Lunin will start between the sticks against Shakhtar.
Lucas Vazquez missed out again on Sunday with a groin problem and the Spaniard has also been ruled out of the competition, but Luka Modric could return to the line-up.
Modric was absent against Osasuna with a minor hip problem, but the experienced midfielder returned to training on Monday and fought for a place in the squad.
However, it would not be a surprise to see the Croatian start on the bench as head coach Carlo Ancelotti will want to manage the midfielder’s playing time during a busy period.
As a result, Federico Valverde, who has largely played on the right of a front three this term, could feature in midfield alongside Aurelien Tchouameni and Toni Kroos.
Should that be the case, Rodrygo could play alongside Karim Benzema and Vinicius Junior in the final third of the pitch, but there could be a defensive change from the weekend.
Eder Militao is indeed looking to replace Antonio Rudiger in the center of the back four, with the latter and Dani Ceballos likely to drop out of the 1-1 draw with Osasuna.
Real Madrid possible starting lineup:
Lunin; Carvajal, Militao, Alaba, Mendy; Valverde, Tchouameni, Kroos; Rodrygo, Benzema, Vinicius
Shakhtar Donetsk possible starting lineup:
Trubin; Taylor, Bondar, Matviyenko, Konoplya; Shved, Bondarenko, Stepanenko, Sudakov, Mudryk; Sikan