Belgium manager Roberto Martinez said Eden Hazard's Real Madrid season is likely over after he suffered a fractured ankle on Saturday.
Hazard suffered the injury in Real's 1-0 defeat to Levante and the club announced the diagnosis on Sunday, but his expected timeline of recovery was not mentioned.
"We are very sad, because this injury will leave him out of action for at least three months.
"A footballer like Eden should always be on the pitch. We have an excellent communication with Real Madrid's medical staff and we are anxious about Eden.
"It's a shame, because it has also happened before an important game as that of Manchester City."
Hazard had only returned in the match prior after missing 16 games after suffering a microfracture in the same ankle on November 26, playing against Paris Saint-Germain in the UEFA Champions League.
The Belgian has also missed the first three matches of the campaign with a hamstring issue he suffered in pre-season. In total, he has played just 15 times for the team since his arrival in the summer, returning one goal and five assists.
Managing Madrid's Lucas Navarrete criticised the timing and the cost of his transfer from Chelsea:
The injury comes at a bad time for Los Blancos. They play Manchester City in the first leg of their Champions League round-of-16 tie on Wednesday before meeting Barcelona on Sunday.
Real's defeat to Levante allowed the Catalan giants to overtake them and establish a two-point lead atop La Liga, so it's vital they at least avoid defeat in El Clasico.
Madrid's final match of the league season is against Leganes on May 24, while the Champions League final will be on May 30, should they make it that far.
As for UEFA Euro 2020, at which Belgium will looking to him as one of their key players, that starts on June 12, with the Red Devils opening their campaign against Russia the following day.