Bowe underwent surgery on Wednesday and now faces a lengthy spell out of action and is expected to miss the Six Nations altogether.
Ireland begin their Six Nations campaign against Wales on February 2 and their five-Test line-up concludes on March 16 against Italy, meaning the wing is effectively out of the competition.
"Tommy Bowe has undergone successful surgery on his knee and is now expected to be out for approximately four months," read an Ulster statement.
"The winger sustained significant lateral ligament damage to his right knee in the closing stages of Ulster's 10-9 Heineken Cup loss to Northampton."
Bowe, who has scored 26 tries in 51 Tests, will be hoping to make a return in time to take part in the British & Irish Lions trip to Australia in the summer, having played a key role in the last tour to South Africa in 2009.
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