Bowe was carried off in the closing stages of Ulster's European defeat to Northampton at Ravenhill as the Belfast side finally lost their 100 per cent record this term.
The former Osprey damaged ligaments and needs an operation, with his province unable to establish a return date until after surgery has been completed.
"An initial scan revealed that he has sustained significant lateral ligament damage to his right knee," read an Ulster statement.
"He will undergo surgery later this week to repair the damage. At this stage it is not possible to put a timescale on how long his recovery period will be.
"A further update on this will be issued following the surgery, when the full extent of the injury will be known."
Bowe hyper-extended after taking a high ball with just three minutes left to play at Ravenhill and is now a serious doubt for the Six Nations next spring.
Ireland's tournament opener in Cardiff is just 47 days away, with Bowe expected to be sidelined for months rather than weeks.
Bowe started all three Tests for the Lions against South Africa three years ago and he is among the favourites for a Test spot when the Lions travel Down Under to face the Wallabies next summer.
But now head coach Warren Gatland will now have to wait with bated breath to see if he recovers in time to put himself in contention for selection.