While United have stressed the move is part of a "planned procedure", they admit it is "frustrating" for the 28-year-old Scotland midfielder, who has made just two short substitute appearances since starting the Barclays Premier League win at Reading on December 1.
A United statement read: " Darren Fletcher will be unavailable for the remainder of this season having undergone surgery to resolve his ulcerative colitis condition."
The statement continued: "We wish to stress this was a planned procedure undertaken at the optimal time having achieved a period of sustained good general health, as illustrated by the fact that Darren has trained with the team regularly this season and been available for selection right up to the operation.
"Whilst it is frustrating for both Darren and the club that he won't be able to contribute further during this campaign, this decision has been taken with our full support in the best interests of his long term health and we look forward to him returning next season with this problem firmly behind him.
"We would be grateful if his privacy could be respected at this time and in the coming months in order to aid his recuperation."
Fletcher has been struggling with the problem since March 2011, although his extended absences from the United side were dismissed by Sir Alex Ferguson as a virus.
However, once it became obvious the midfielder could not play his way through the injury, United eventually confirmed the extent of the condition and confirmed he was going to take a full break.
Fletcher even missed pre-season training last summer to ensure his comeback was a success, making his reappearance as a substitute against Galatasaray at Old Trafford in September.
Although he initially eased his way back into the first-team fray, the Reading game represented his third start in four games and he spoke optimistically about his role in the coming weeks.
Instead, after another substitute appearance the following Wednesday against CFR Cluj, matches against Sunderland and Swansea - where he did not come off the bench - and Newcastle on Boxing Day, when he was introduced for the final minute for his 10th and final appearance of the campaign, he was not seen again.
When questioned about Fletcher's absence at a time when matches were being encountered every three days, Ferguson said the pitches were too heavy for the Dalkeith-born player.
However, when he did not make the bench for last night's FA Cup tie with West Ham, when Ferguson made 10 changes to his starting line-up, it was obvious there was a more significant problem.
Now Fletcher, one of the most popular players in the United dressing room, is once again facing an extended period on the sidelines - and question marks about his future.