Channel 4 has confirmed that O'Leary, who also hosts The X Factor on ITV1, will not return to present Big Brother's Little Brother when series nine of the summer show gets underway next year.
"It is with great regret that my time on Big Brother will come to an end after Big Brother: Celebrity Hijack," O'Leary said in a statement. "For the last seven years I've had the time of my life working on Big Brother's Little Brother, from our broom cupboard days to the all singing and literally all dancing show we make now.
"But this summer's work commitment of BBLB and The X Factor has proven to me that to do both shows is impractical if not impossible. I want to thank Channel 4 and the Big Brother family for all their support and for the opportunity to present a live show that I love with all my heart."
In August, O'Leary dismissed suggestions that he was planning to leave Big Brother's Little Brother despite having been advised by Simon Cowell to concentrate on The X Factor.
Big Brother commissioning editor and head of E4 Angela Jain said: "BBLB has been Dermot's little baby from the start. He was our first choice and the best choice. We will miss him and all the laughter and professionalism he has brought with him. I'm delighted we can hold on to him a little longer because he has chosen to host Big Brother: Celebrity Hijack as his Big Brother swansong."