Ubisoft has confirmed that Patrice Désilets "has decided to take a creative break from the industry".
Earlier US magazine Game Informer reported that the Ubisoft Montreal creative director had left the company.
Désilets had been intimately involved with the Assassin's Creed franchise since its inception and was a pivotal figure in the second game's path to success in 2009.
"With his role on project essentially done, Patrice Désilets has decided to take a creative break from the industry and is no longer working on Assassin's Creed Brotherhood," Ubisoft told Game Informer after initially dismissing the story as "rumour and speculation".
Assassin's Creed: Brotherhood is the third major Assassin's Creed game but is not seen as the end of the proposed trilogy of releases.
It is due out in late 2010 and holds its focus on the second game's Renaissance protagonist, Ezio Auditore, despite developments in the larger meta-story that would suggest Ezio's role is spent.
We're seeing Assassin's Creed: Brotherhood at E3, so we'll be sure to ask what happened to Désilets.
Earlier this year Far Cry 2 director Clint Hocking announced he was leaving Ubisoft after nine years.