A source close to the actress revealed to Us Weekly that Witherspoon is currently negotiating to join Bublé on an upcoming musical project.
It is not yet clear if the track will appear on Bublé's next album, a follow-up to 2011's US and UK chart-topping LP Christmas.
Witherspoon famously recorded four songs for the soundtrack to her 2005 film Walk the Line, in which she played Johnny Cash's wife June Carter.
The actress earned wide praise from critics and audiences alike for her performance in Walk the Line.
Witherspoon won not only the 'Best Actress' Academy Award, but also a Golden Globe and a BAFTA.
Her spokesperson has not commented on a potential Bublé duet.
Listen to Reese Witherspoon sing 'Juke Box Blues' in Walk the Line below: