Zidane instead used the more defensive Mateo Kovacic from the off in an attempt to limit Lionel Messi's influence, which worked in the first half but had less effect in the second as Barca netted three times to run away with it.
Speaking to beIN Sports after the match, the under-fire Frenchman said: "I have to make decisions. The idea was to keep an eye on Messi, and Mateo did well. We made a decision and that's it.
"I'm making decisions as a coach. The decision was Kovacic on the pitch and Isco on the bench at the start. Then, because of how the match went, I was not able to use Isco.
"I had to use Nacho because of the red card [for Dani Carvajal] and had two changes left with one player less. That changes the game. I'm the coach and it's always going to be like that while I'm here.
"I will not regret anything. If you score in the first half the match is different. I know I will take the criticism, but that's football, and it will not change how I think. I make these decisions and I accept what happens."
Meanwhile, Isco has hit out at media suggestions that he refused to warm-up during the second half of his side's costly home defeat.