Fletcher seemed to have conquered his colitis problem when he managed to get through three games out of four at the end of November. But since starting at Reading on December 1, the 28-year-old has managed just a couple of brief substitute appearances before undergoing surgery that may help him conquer the chronic bowel condition for good.
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 Scotland international captain could not play his way through the injury, United eventually confirmed the extent of the condition and that 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 re-appearance as a substitute against Galatasaray at Old Trafford in September.
However, despite speaking optimistically about his recovery, after a substitute appearance against CFR Cluj immediately after the Reading game, a one-minute run-out against Newcastle on Boxing Day proved to be his 10th and final appearance of the campaign.