Luis Enrique could not guarantee Isco a place in his next Spain squad due to his lack of minutes at Real Madrid.
Although he has been an ever-present in recent years for Spain, Isco has had a difficult season at club level.
The playmaker has not started a LaLiga fixture since Julen Lopetegui's final match in charge of Madrid, the 5-1 Clasico demolition by Barcelona.
Under Santiago Solari, Isco has had to be content with a role as a substitute or only starting in other competitions and he failed to even get off the bench in Sunday's 4-2 win at Espanyol.
Speculation has suggested he is happy to stay at the club until the end of the season to see if Solari stays, but the 26-year-old's status in the Spain squad could be affected before that, with their Euro 2020 qualification campaign starting in March.
Speaking to Movistar, Spain boss Luis Enrique said: "Right now, I do not know if I will call him up, we will treat each case individually.
"There are still two months left for the list, though I would prefer that he was playing more minutes, like those who do not play as much [for the national team], but football is like that."
One Madrid and Spain player Luis Enrique remains impressed with, however, is Sergio Ramos.
The centre-back has scored five times this season and, although Madrid's record of 26 goals conceded is worse than eight other clubs, Luis Enrique insists there can be no doubt about Ramos' abilities.
"He's not [just a] centre-back, he's a midfielder, a forward," said Luis Enrique. "Whatever he wants to be, he will be.
"His level is beyond doubt, his scoring data is amazing for a defender, who has the spirit of an attacker."