Los Blancos will again be without the services of Lucas Vazquez, Dani Carvajal and Ferland Mendy this weekend through injury, while Toni Kroos is unavailable, having recently tested positive for coronavirus.
Raphael Varane and Sergio Ramos have both trained this week as they bid to be available; the former is likely to feature in the starting XI, but the latter will allegedly only be considered for a spot on the bench.
Nacho could switch across to left-back to allow Varane to return to the side, but there are not expected to be any changes in the middle of the park, with Federico Valverde joining Luka Modric and Casemiro.
Karim Benzema is a certainty in the final third of the field, but Zidane has decisions to make around the Frenchman as there are plenty of options for change.
Vinicius Junior seems likely to be given the nod over Eden Hazard on the left, while Marco Asensio could be handed a start on the right ahead of Rodrygo.
Varane's return also opens up the option of a 3-5-2 formation, but Kroos's absence from the middle of the park means that Zidane is expected to select a 4-3-3 against Villarreal, who are battling for fifth position.
Real Madrid possible starting lineup: Courtois; Odriozola, Varane, Militao, Nacho; Valverde, Casemiro, Modric; Vinicius, Benzema, Asensio