The Spain international will be out of action for an estimated six weeks after breaking a thumb during his side's 1-1 draw with Valencia on Wednesday
The keeper was forced to leave the pitch after 17 minutes of play at Mestalla, and the club have now announced that he has sustained the injury, meaning he will miss the Champions League tie with Manchester United next month.
"After carrying out initial X-rays at the La Moraleja Sanitas Hospital, it has been confirmed that the footballer Iker Casillas has suffered a fracture at the base of the first metacarpal on his left hand," a statement on the Madrid website reads.
"It will be assessed again by a specialist later today to decide what treatment will be followed."
The knock will keep Casillas out of action for an estimated six weeks, meaning he will certainly miss the clash with Untied in the Spanish capital.
Additionally, the 31-year-old is doubtful for the return against the Red Devils, while he could also be forced out of the Clasico versus Barcelona on March 2.