France forward Benzema has not featured since picking up a knock in the loss to Valencia on November 8, and was absent as Real returned to action following the international break with a draw at Villarreal.
There was hope that he would be fit to link up with the squad for the trip to Inter on Wednesday, but his name was absent from the 21-man list.
While Zidane is without his most potent attacking weapon and most experienced defender, he can call upon Casemiro.
The Brazilian has not featured since testing positive for coronavirus prior to the international break.
Casemiro linked up with the Madrid squad ahead of the Liga game with Villarreal on Saturday, but he was deemed to not be sharp enough for match action.
The 28-year-old’s return is a huge boost to Zidane as he offers control in the middle of the park, which will be needed on the night in Milan.
Real travel to Inter occupying second place in Champions League Group B, with a win, a draw and a loss to their record from three games.
The match is not a must win for Real, but defeat would be a huge setback for their chances of reaching the knockout stages - and Casemiro’s calming presence will be of major significance.
An intriguing name on the squad list is Hugo Duro, the 21-year-old forward who is on loan at the club from Getafe.
With Benzema out and Luka Jovic absent after testing positive for coronavirus, Duro has been given the nod to travel.
He joined the club earlier this year and was expected to spend the season with the Castilla squad, but the lack of options has prompted Zidane to include him and he could make his Real debut in a Champions League tie.