Byrne, 30, who has won 38 caps and toured South Africa with the 2009 British and Irish Lions, will follow his Ospreys and Wales colleague James Hook to France after the World Cup in New Zealand later this year.
Hook, a rival for Byrne's number 15 shirt in Friday night's Six Nations opener against England, announced last week he would be joining Perpignan next season.
The Ospreys confirmed they had "reluctantly agreed" to Byrne's request that he be released early from his existing contract with the region, which runs until 2012.
Ospreys managing director Mike Cuddy said: "It is extremely disappointing to lose a player who hails from the region, and who has been, and continues to be, an excellent servant to the Ospreys.
"Our determination to keep Lee at the Ospreys meant that we fought hard to keep him here, turning down a similar request 12 months ago.
"But unfortunately, the circumstances are such that we now find ourselves in this position where we have reluctantly agreed to release Lee, given his desire to take on a fresh challenge following the Rugby World Cup later this year."
Byrne, who joined the Ospreys from the Scarlets in 2006, added: "I will be sad to leave my home region, but this was too good an opportunity for me to turn down at this stage of my career.
"I am excited about what the future holds for me in France, and the challenges that lie ahead for me. I am extremely thankful to the directors of the Ospreys for the way that they have handled this, allowing me to look ahead to what will be a fantastic experience for me.
"In the longer term, the Ospreys is my region, and I would like to think that I will be able to return here before my career is over."