The Real Madrid midfielder will play no part in Spain's friendlies with England and Belgium due to a muscle injury.
Isco has withdrawn from the Spain squad due to a "strained muscle," it has been confirmed.
The Real Madrid attacking midfielder was included in Vicente del Bosque's group for the friendlies against England and Belgium this month.
However, after experiencing discomfort and failing to complete training with the rest of the squad he has opted to return to his club.
"[Isco] carried out an individual training session, separate from the team, due to the discomfort felt upon arriving to the practice," a statement said.