The 21-year-old has accused European football's governing body of "embarrassing" double-standards after the Liga side's ban from continental competition was upheld.
On Tuesday, the Court of Arbitration for Sport (CAS) upheld the initial sanction imposed by European football's governing body which suspends Los Boquerones from competing in the UEFA Champions League or Europa League after they failed to adhere to Financial Fair Play regulations.
Isco, who is currently on Spain Under-21 duty in the European championship in Israel, has accused UEFA of being more severe with Malaga than it would be with other clubs who commited the same offenses.
"It is embarrassing and shabby. It is completely unfair that they have treated Malaga different than many other teams with many more irregularities and debts," Isco wrote on his Twitter account. "They have taken away what we have earned on the field. Neither the players nor fans deserve this. I have no more to say."
The Andalusians, whose sixth-placed finish in the Liga standings last season would have seen them gain entry to the Europa League, will now be stripped of their place in favor of either Sevilla or Rayo Vallecano.