Although the Belgian started Los Blancos' weekend match against Osasuna, which ended in a disappointing 0-0 draw, he has only just returned from yet another injury, so Zidane may be keen to keep him from playing two games within six days.
Should Hazard drop out, expect Vinicius Junior to come in on the left-hand side of the front three alongside Karim Benzema and Marco Asensio.
There is, of course, the possibility that Hazard will remain in the starting XI if he is deemed fit enough.
Injuries and the form of Luka Modric have seen Fede Valverde lose his place as a starter for Real Madrid over the past few months, but Zidane could use this cup game as an opportunity to give the Uruguayan some deserved minutes.
Modric might then be relegated to the substitute's bench.
Toni Kroos and Casemiro will likely retain their places from the weekend.
Dani Carjaval would have been available for this game after serving a suspension, but he has collected a hamstring injury, which will see Lucas Vazquez once again deputise at right-back as he has already done many times this season.
For the rest of the defence, it should be the same as Saturday's draw, with Sergio Ramos partnering Raphael Varane in the middle and Ferland Mendy at left-back.