James Rodriguez will undergo surgery after fracturing the fifth metatarsal in his right foot during Real Madrid's 2-1 victory over Sevilla.
Real opened up a four-point advantage over nearest rivals Barcelona at the top of La Liga by beating Sevilla on Wednesday, with Rodriguez opening the scoring in the 12th minute.
However, the Colombia forward was forced from the field 15 minutes after finding the net with a diving header and coach Carlo Ancelotti revealed in his post-match interview Rodriguez will miss Saturday's derby against Atletico Madrid.
A subsequent update on Real's official website confirmed the 23-year-old requires an operation.
It read: "Following tests on James Rodriguez for the medical services of Real Madrid in the Hospital Sanitas La Moraleja, he was diagnosed with a fracture of the fifth metatarsal of his right foot.
"The player will undergo surgery in the coming hours."
Rodriguez is in his first season at The Santiago Bernabeu, having moved from Monaco in a high-profile transfer following his outstanding displays for Colombia at the 2014 World Cup.
Wednesday's goal against Sevilla took his tally to 12 for the season in all competitions and saw Rodriguez score for the second successive game in the absence of the suspended Cristiano Ronaldo.
Ballon d'Or winner Ronaldo will return from his ban to face Atletico on Saturday, but Rodriguez now faces several weeks on the sidelines.