Eden Hazard will miss the first leg of Real Madrid's Champions League last-16 tie against Manchester City after breaking his ankle.
The 29-year-old limped off during Saturday's 1-0 defeat at Levante in La Liga. It was only his second match since returning from another ankle injury which had kept him out of action for almost three months.
Real Madrid assessed the injury overnight and confirmed on Sunday that Hazard had suffered a fracture. They have been unable to put a time frame on his period of recovery.
A club statement said: "Following the tests carried out on our player, Eden Hazard, by the Real Madrid medical department, he has been diagnosed with a fracture to his right distal fibula."
Real Madrid's next two games are at home to Manchester City in the Champions League on February 26 followed by El Clasico against Barcelona at the Bernabeu on March 1.
Real's first defeat in the league since October saw them fall to second place in La Liga on 53 points after 25 games.
Barcelona replaced them at the top of the table on 55 points after hammering Eibar 5-0 earlier in the day, thanks to four goals from Lionel Messi.
Pep: Laporte can play 90 vs Real
Pep Guardiola is confident Aymeric Laporte is ready to play 90 minutes against Real Madrid on Wednesday night despite the defender asking to be substituted during Saturday's 1-0 win at Leicester.
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Laporte was replaced by Nicolas Otamendi after 57 minutes of Saturday's match, his third appearance since his return from a long lay-off with a knee injury.
Guardiola said there was no fresh injury problem for the Frenchman, but the pace of Leicester's attack was a tough test for a player still rediscovering his rhythm.
"He asked me to be subbed," Guardiola said. "He's not injured. We cannot forget he has been out for four or five months injured. They run a lot, (Jamie) Vardy, Kelechi (Iheanacho), (Harvey) Barnes, they are all so fast.
"It was quite different against West Ham (on Wednesday) where they was only one striker so it was easier to control, but he's OK."
Asked if Laporte was ready to play the full match at the Bernabeu on Wednesday, Guardiola simply said: "Yes".
Laporte has made a gradual return to action from the knee injury suffered against Brighton on August 31.
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