The 26-year-old will miss Saturday's clash with arch rivals Atletico Madrid following surgery on Tuesday afternoon.
The reigning Champions League winners did not put a timescale on Isco's recovery, but said in a statement on Wednesday morning: "Our player Isco has been discharged from hospital today.
"From now on, he begins his recovery process under the supervision of Sanitas Real Madrid Medical Services."
Isco is expected to be out for around four weeks and is also a doubt for next
month's El Clasico with Barcelona at the Nou Camp.
The midfielder has been a mainstay in Los Blancos' team since Julen Lopetegui replaced Zinedine Zidane as head coach in the summer, featuring in each of the seven matches in all competitions and has scored two goals in the process.
Lopetegui, speaking at a press conference on Tuesday, said: "He had pain this morning and has to have an operation. Hopefully everything goes well and he recovers as soon as possible.
"We wish him a speedy recovery and we'll think about the solutions and those who can play because we have the utmost confidence in them."