Isco has been discharged from hospital after undergoing surgery, Real Madrid have confirmed.
The Spain star experienced stomach pains on Tuesday and was diagnosed with acute appendicitis.
After having surgery, Isco will definitely miss Wednesday's LaLiga trip to Sevilla, with Madrid giving no timescale for his recovery.
But barring a miracle recovery Isco is almost certain to be unavailable for Saturday's El Derbi against Atletico Madrid at the Santiago Bernabeu.
"He begins his recovery process under the supervision of the Sanitas Real Madrid Medical Services," Madrid said in a brief statement.
Reports have indicated Isco could be out for around a month, ruling him out of Champions League ties against CSKA Moscow and Viktoria Plzen.
Speaking at a news conference on Tuesday, Madrid head coach Julen Lopetegui was hopeful Isco would not be out for too long.
"Hopefully it's a speedy recovery," he told reporters. "When a player's out it's always bad news and we wish him a speedy recovery.
"We've got a good squad and somebody else will have to play. I have total confidence in the rest of my players.
"I have not been able to talk to him. He's about to go into surgery. I hope he can quickly get back into shape."