Speaking after netting a hat-trick for La Roja in their 6-1 win over Argentina in Madrid on Tuesday night, Isco suggested that Zidane has not shown enough belief in him.
The 25-year-old has been in and out of Los Blancos' starting lineup this term, despite a positive return of five goals and five assists in La Liga, and has admitted his displeasure at often being overlooked.
Asked to comment on Isco's remarks, though, Lopetegui simply stressed the importance of his players being happy.
"I'm not going to talk about Real Madrid and Zidane's decisions," he told reporters at his post-match presser. "I haven't learnt anything new with Isco's performances; I'm so pleased to have him with us.
"I hope that he will be happier with his club in the next two months and then join up with us again."
Isco has started 25 games for Madrid in all competitions this term and featured a further 11 times from the bench.