Real Madrid centre-half Pepe limped out of his side's 4-1 win over Alaves on Saturday, nursing a leg injury.
The Portuguese defender is set to join fellow centre-back Sergio Ramos in having an extended spell on the sidelines, as reported by theBBC, as he is set to be ruled out for several weeks.
LaLiga Ballon d'Or nominees:
G.Bale
C.Ronaldo
D.Godin
A.Griezmann
A.Iniesta
Koke
T.Kroos
L.Messi
L.Modric
Neymar
Pepe
S.Ramos
L.Suarez pic.twitter.com/BB2edgq4de
The injury, described as a "grade two muscle injury in the femoral biceps of his left leg", looks set to rule Pepe out of crunch clashes with La Liga rivals Atletico Madrid and Barcelona, in the coming weeks.
The report suggests that Pepe could be out for between four to six weeks, making him a major doubt for the Madrid derby on 19 November, and he will struggle to make El Clasico in early December.
The loss of both first-choice centre-backs will no doubt be a major blow to Real Madrid manager Zinedine Zidane's plans, with his side sitting top of the table, but with just three points separating the top four clubs.
The injury blow comes just after Pepe was named on the 30-man shortlist for the Ballon d'Or, following a 2015-16 season in which he won both the Champions League with Real, and Euro 2016 with Portugal.
The 33-year-old divides opinion due to his theatrical antics on the field, but there is no doubt that he was a crucialpart of the rearguard action that saw Portugal defeat the odds to clinch the European Championships.