Ulster wing Tommy Bowe has been ruled out for six months after having surgery on a knee injury on Monday.
The 31-year-old is unlikely to play again this season after suffering the injury during Ireland's World Cup quarter-final defeat by Argentina.
Ulster Rugby confirmed Bowe suffered posterior cruciate ligament and meniscal damage and will miss the Six Nations and European Champions Cup.
Lock Iain Henderson needs an operation on his hand and is out for six weeks.
Jared Payne, the third Ulster player to require an operation after Ireland's World Cup campaign, had a fractured foot stabilised through surgery but it is not yet known how long he will be out of action.
Bowe injury worse than anticipated
Ulster were expecting Bowe to be on the sidelines for around two months, but the injury has turned out to be more serious than originally thought.
An Ulster Rugby statement confirmed the player will be ruled out for "at least" six months, which means his season is effectively over.
Monday's operation was described by the province as "successful" but there will be doubts over the player's international future following this latest injury setback.
He is now certain to miss Ireland's attempt to win a third Six Nations Championship in a row next spring, as well as Ulster's upcoming European Champions Cup campaign.
In another serious blow to Ulster's European hopes, Henderson is due to have surgery on Tuesday to stabilise a joint in his hand which was also damaged during Ireland's World Cup defeat by the Pumas.
The 23-year-old second rower was one of Ireland's best performers in the World Cup but will now have to sit out Ulster's European Cup matches against Oyonnax, Saracens and back-to-back fixtures with Toulouse before Christmas.
"We've had a bit of a war of attrition on the back of the World Cup," admitted Ulster coach Neil Doak.
"It's a little bit frustrating.
"The resources are going to be stretched week after week and it definitely is a blow to us to be without that experience and quality for such a long period of time."
Doak confirmed Ireland assistant coach Les Kiss will take up his post as Ulster's Director of Rugby on a full-time basis on Monday.