James and Bullock's marriage first hit the rocks in March when James was accused of carrying out an 11-month affair with tattoo model Michelle "Bombshell" McGee while Bullock was in Atlanta filming The Blind Side -- for which recently won the Oscar for Best Actress.
"You cheated on your wife?" asked Nightline's Vicki Mabrey.
"Yup," replied James.
"The headlines say you're the most-hated man in America..." said Mabrey at one point in the interview.
"I think it's the most-hated man in the world now," responds James.
James will also be asked questions including "why did he throw away a seemingly perfect life and the perfect wife, what did he really go to rehab for, and what role will he play in the life of Louis, the baby boy Bullock recently adopted," according to ABC.
James' Nightline interview will air Tuesday, May 25 at 11:35PM ET/PT on ABC.