The Brazil international reportedly picked up a knock in Friday's training session ahead of Saturday's visit of Real Sociedad and has now been diagnosed with traumatic arthritis.
And the 25-year-old, who missed five games in September because of a hamstring problem, now faces another spell on the sidelines after being excluded from Real's squad for the game against Sociedad.
No timetable has been set for Marcelo's return, leaving manager Carlo Ancelotti short of options at left-back after Fabio Coentrao sustained an ankle injury in the 3-2 win over Rayo Vallecano last weekend.
A statement on Real's official website read: "Following examinations and scans carried out today Marcelo at Sanitas-La Moraleja hospital, he has been diagnosed with traumatic arthritis in the left knee."
Ancelotti's men sit six points adrift of league leaders Barcelona ahead of the clash with Sociedad, and the Italian is expecting the Basque outfit to present a difficult challenge.
"Real Sociedad is a good team with a good attitude," he said.
"They're very dynamic and have fast players. It won’t be an easy match. They already proved against Manchester United that they can play major games and it's a really good test for us because we need to play well and with intensity."
‘I trained at Spurs and thought they’d give me a chance. But I received a letter thanking me but saying they didn’t think I was good enough – I was gutted’: How Tottenham missed out on signing Wales legend John Toshack
'People around the world know me because of my goal at Chelsea. I still can’t explain it, though. Drogba even asked me, 'Who are you? What did you eat?"' Newcastle cult hero Papiss Cisse recalls iconic strike at Stamford Bridge
