The Swansea-based outfit have announced that Cuddy will relinquish his role with immediate effect and no longer be involved in the day-to-day running of the business.
Cuddy has been a key figure at the Ospreys since they were founded nine years ago when Welsh professional rugby was restructured.
His duties will be taken on by current joint managing director, former Wales full-back Roger Blyth, and Ospreys chief operations officer Andrew Hore.
In a statement, the Ospreys said: "In common with the other regional sides in Wales, Ospreys Rugby has faced a significant number of challenges in the last few years including financial difficulties, some of which have been well documented.
"Following the successful conclusion of a number of initiatives which directors and shareholders have been involved in, Ospreys Rugby can now look forward confidently to a more stable future.
"Recognising this, and given the other commitments of some of the principal people involved in managing the organisation, Ospreys Rugby has taken the opportunity to reorganise its management structure.
"Mike Cuddy will step down from day-to-day management of the rugby operation and will also relinquish his position as a joint managing director with immediate effect.
"Roger Blyth and Andrew Hore will between them assume the duties previously undertaken by Mike Cuddy.
"Ospreys Rugby wish to thank Mike Cuddy for the efforts he has put in over the years since the region's formation."
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