The winger underwent 'successful surgery' on his knee on Wednesday, and Ulster say he is facing a lay-off of up to four months.
That means the 28-year-old will miss the province's festive derbies in the RaboDirect PRO12 and the conclusion of the Heineken Cup's pool stages next month.
Bowe is also likely to be sidelined for all of Ireland's RBS 6 Nations matches. The campaign begins with a trip to the Millennium Stadium to face defending champions Wales on Saturday, February 2.
It is a cruel blow for the Monaghan man who was enjoying his first season back in Ulster colours, helping the province string together 13 successive wins across the league and Heineken Cup.
He has scored three tries in eight appearances so far this season for Ulster, and also dotted down twice against Argentina in the GUINNESS Series last month - taking his excellent Irish try-scoring haul to 26 in 51 Test matches.
Bowe was the 2012 Six Nations' top try scorer with five in five games. He played in all three Tests during the 2009 British & Irish Lions tour to South Africa, and expects to be fully for the Lions' trip to Australia next summer.