The European champions sit 15 points behind Barcelona heading into the weekend's La Liga games and the Catalan side will secure the title if they draw with Deportivo on Sunday, regardless of Madrid's result.
Zidane's team are still out to defend their Champions League title, however, and can book their place in a third consecutive final if they protect the 2-1 lead they hold over Bayern Munich in the second-leg of their semi-final tie on Tuesday.
In anticipation of the crucial clash, Ronaldo will play no part of Madrid's match with 16th-placed Leganes, while central defender Raphael Varane has also been rested.
Defender Dani Carvajal and midfielder Isco are also out after both suffered injuries in the first leg in Munich, while Nacho is still out with a muscle problem.
Although Marcelo, Luka Modric, Casemiro and Toni Kroos are all in the squad, they are expected to be left out of the first team, but attackers Gareth Bale and Karim Benzema could be included after they were given a place on the bench in midweek.
Achraf Hakimi, Theo Hernandez and Jesus Vallejo are expected to start in a much-changed defence.