Real Madrid have confirmed that Casemiro has suffered a fracture to a bone in his left leg.
The Brazilian midfielder picked up what at first looked to be a minor knock in the 2-0 win over Espanyol and was substituted out of precaution.
He was unable to feature in Wednesday's 1-1 draw with Villarreal but was fit enough to complete an individual training session indoors less than 24 hours later.
Following tests on the problem, however, the club has identified a more serious injury than first feared.
"Following tests carried out today on Casemiro at the Sanitas La Moraleja University Hospital, he has been diagnosed with a fracture to the central third of his left fibula," a statement released on Madrid's official website read. "His recovery will continue to be assessed."
Initial reports in Spain suggest Casemiro will be sidelined for approximately three weeks, meaning he is expected to miss the matches against Las Palmas, Borussia Dortmund and Eibar.
The 24-year-old, who has made five appearances in all competitions for Madrid this season, is also likely to miss Brazil's World Cup qualifiers against Bolivia and Venezuela next month.
Teammate Marcelo, meanwhile, is reportedly facing two weeks out after picking up a calf injury against Villarreal.