Romeu was replaced with Moussa Djenepo after 70 minutes when he suffered the injury in Southampton’s 3-0 loss to Leeds United in the Premier League on Tuesday.
The 29-year-old Spaniard joins a growing list of injuries for Southampton that has threatened to derail their season after an impressive start.
Southampton briefly went top of the Premier League back in November but have now slipped to 14th position on the table after losing seven of their last eight games, including a 9-0 reverse to Manchester United earlier this month.
The likes of Theo Walcott, Kyle Walker-Peters, Ibrahima Diallo, Will Smallbone, Michael Obafemi and Takumi Minamino are all currently on the treatment table.
Speaking at his press conference on Friday ahead of Monday’s game against Everton, Southampton manager Ralph Hasenhuttl said: “Oriol Romeu's season is over.
“Surgery means months out after he fractures his ankle. It will take maybe three months that he is out.”
“It is a strange injury. Only a bad step from the right foot. I don’t know if there was an injury before or they don’t know it.
“Some things like this can happen very quickly. Maybe when you have a little bit of stress and a lot of games happen in the past, but he was also out and was just coming back. It’s strange.”
Romeu, who joined Southampton from Chelsea in 2015, has made 20 appearances in the league this season, scoring one goal.
