The attacker was replaced 69 minutes into the league contest after struggling to make an impression in Barcelona.
Isco has only started four La Liga matches in 2018 amid a disappointing run of form, but Zidane said that 'everyone loves' the Spain international when questioned on his recent struggles.
"I don't think it was anything abnormal," Zidane told reporters. "He wasn't happy about coming off, but that's the case with most players. He has a great attitude, trains well and everyone at the club loves him.
"There's nothing to worry about there. If a player is angry about being substituted then that is normal."
Isco has scored seven times and registered six assists in 36 appearances for Madrid this season.