Bowe touched down five times during the 2012 RBS 6 Nations and his absence will make Ireland's already foreboding trip to world champions New Zealand even more daunting.
The 28-year-old was diagnosed with high blood pressure earlier this year which was caused by a haematoma that is pushing into his left kidney.
Surgery will keep him out for the rest of the season with Ospreys and he could even miss the start of next season when he will be in Ulster colours.
An Ospreys statement read: "After considerable consultation with specialists in both Ireland and Wales, Tommy has opted to go down the route of surgical removal of the haematoma in an effort to solve the problem.
"He is being operated on in Ireland today, before returning to Wales post-op to convalesce. Because of the surgery, he will not be able to play any further part for the Ospreys this season, ahead of his return to Ulster for next season. Recovery time post-operation is unclear, but he could be sidelined for up to four months."
It marks a disappointing end to Bowe's spell at the Liberty Stadium where he has helped establish himself as one of the northern hemisphere's deadliest wingers.
His strike rate in the RBS 6 Nations stands at 14 tries in 24 appearances and he admitted it was a wrench to leave South Wales.
He said: "Having confirmed my move to Ulster during the Six Nations I was really looking forward to returning to the Liberty Stadium for the end of season run-in, to help the Ospreys towards hopefully another league title, and also, to say a big thank you to the region's incredible fans for all the support they've given me over the last four years.
"Obviously, this news unfortunately means that I won't get to wear the Ospreys shirt again, but it's important that I get this problem sorted as soon as possible.
"Hopefully, the Ospreys will have a home semi-final and final in May so that I can still get down to the Liberty to say farewell to the supporters."