The New Zealand ineternational was forced off with the problem during last weekend's 1-1 Barclays Premier League draw against Birmingham and manager Steve Kean revealed there was no option but for Nelsen to go under the knife.
The centre-back partnership between Nelsen and captain Christopher Samba has been one of Blackburn's main strengths and the news is a major blow to their survival hopes.
Missing man: Ryan Nelsen (C) is out for the rest of the season due to a knee injury
Kean said of the operation: 'It went well. The surgeon was happy about it and he had a full clearout.
'There were a lot of little bits of floating debris in his knee that he's been in a lot of pain with. He couldn't manage to go on.
'We're hopeful he'll be back in time for pre-season.'
With Rovers only three points above the relegation zone heading into Saturday's trip to Everton, Kean can ill afford such setbacks, but he cited the return of youngster Phil Jones from his own knee injury as a saving grace.
Back in action: young defender Phil Jones is ready to return for boss Steve Kean
'Fortunately for us we lose Ryan at a time when Phil Jones is back fully fit,' Kean said, speaking to the club's official website.
'He's slotted back in there and looked like he'd never been away from central defence, so that is fantastic for us, but it is unfortunate that we lose Nelly.'
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Explore more:People: Ryan Nelsen, Christopher Samba Places: Birmingham, New Zealand