The Belgium national team captain was replaced by Vinicius Junior in the 67th minute in a defeat that saw Zinedine Zidane’s men replaced by Barcelona at the top of the table ahead of next Sunday’s crunch clash between the two teams at the Santiago Bernabeu.
Hazard only returned to action last week against Celta Vigo after almost three months out with an ankle injury.
Following tests carried on the former Lille attacker by the Real Madrid medical team, Hazard has been diagnosed with a fracture to his right distal fibula.
A club statement released on Sunday read: "Following the tests carried out today [Sunday] on our player, Eden Hazard, by the Real Madrid medical department, he has been diagnosed with a fracture to his right distal fibula.
"His recovery will continue to be assessed."
Although Real Madrid have not confirmed how long Hazard will be out for, reports in Spain suggest he could be out for another two months.
Hazard joined Real Madrid in a big-money move from Chelsea in the summer but is yet to set the Santiago Bernabeu alight with the exceptional performances he is usually associated with.
The 29-year-old has scored just one goal and provided one assist from 15 appearances across all competitions for Los Blancos this season.