Ronaldo was taken off by Zidane immediately after substitute Isco had struck with nine minutes left to put Madrid back in front at Ciutat de Valencia on Saturday.
But a lapse in defensive concentration subsequently allowed Levante to score their second equaliser of the game one minute from time, substitute Giampaolo Pazzini striking on his debut for the club.
Madrid's latest setback leaves Zidane's men 18 points behind Liga leaders Barcelona and with an upcoming Champions League tie against Paris Saint-Germain growing in importance, with the competition their only realistic chance of winning another trophy this season.
After the match, Zidane insisted Ronaldo's substitution was not fitness-related.
"No. It was planned to change him, and that's all," Zidane told beIN SPORTS after the match.
"We had the game under control, the most difficult is to score goals. We got to 2-1, but in the end, two mistakes cost us the two goals.
"This year is being difficult for us. We cannot put three or four results together. I am not happy with the result. We were in control of the game, above all the first half, so not happy, of course.
"The pity is that after we scored our second goal, we were not able to keep hold of the ball, and defensively we were not good."
Asked again about Ronaldo in his post-match press conference, Zidane added: "I changed him as I wanted another player a bit more in the middle of the pitch, to defend with Marco Asensio and Karim [Benzema]."
1 - Levante haven't lost in any of the two games in a La Liga season against Real Madrid for the first time. Reward pic.twitter.com/RjAZscBKxD— OptaJose (@OptaJose) February 3, 2018
Zidane previously indicated he believes his job is on the line when Madrid host Paris Saint-Germain in the last 16 of the Champions League on February 14, but the Frenchman appeared to row back on his comments after Madrid missed the chance to climb above Valencia into third.
"I just think about the next game, nothing else," a frustrated Zidane said.
"La Liga will not be over until the end. There are a lot of points, and two more today, even when we had the game under control. We should have won a third consecutive game, but we did not.
"When it was most difficult we got the second. Then we must be clever, avoid the second goal, and we did not. We were not focused, and that is hard to take as it is two points lost.
"That means we must work even harder. This is football, and the opponent can make things difficult for you. But we could have avoided their second goal. That annoys me, as we have worked on that, and knew they could counter-attack."