The Madrid playmaker hit a treble in Tuesday's 6-1 demolition of Argentina in Madrid, Spain inflicting the joint-worst defeat in Albiceleste history.
Isco is far from an automatic starter at Madrid, despite contributing five assists and five goals in La Liga this season, and the midfielder appeared to aim a barb at Zidane after the game, noting the confidence he feels from Lopetegui helped him to star with a thrilling performance.
Lopetegui, however, said Isco's display was down to the player rather than himself, although the Spain coach is hopeful the 25-year-old will keep up his fine form at club level.
"I'm not going to discover anything new about Isco," said Lopetegui. "Nor the feeling that comes from having him, nor his performance with us.
"We want him to be happy to face the World Cup with enthusiasm, I do not give him the confidence.
"I'm not going to talk about Real Madrid and Zidane's decisions. I'm not going to fight with anyone because he's happy with us and has euphoria."
While Spain sent a message to their World Cup rivals with a dominant dismissal of Argentina, who were without the injured Lionel Messi, Lopetegui cautioned that winning in a friendly counts for little, regardless of the margin of victory.
"I have congratulated the players and thanked them," added Lopetegui. "The World Cup has not started yet.
"We have won against a team with a fantastic history and a finalist of the last World Cup. It is a magnificent team, it is true that they had casualties, because Messi, [Sergio] Aguero and [Angel] Di Maria are decisive for them
"We will start the next World Cup with zero points. It is a friendly, it is not equal to a World Cup match. You have to be happy."