On 6 June 2008, Holmes turned down Leeds United and Nottingham Forest to instead sign for Championship side Southampton as their first summer signing. He was attracted by the promising youth set up under new coach Jan Poortvliet, chairman Michael Wilde and the size of the club. Holmes made his debut for Southampton in the opening game of the 2008–09 season against Cardiff City. Holmes was substituted in the second half, replaced by Bradley Wright-Phillips, as Southampton lost 2–1. Holmes scored in his second game with Southampton, as they defeated League Two side Exeter City 3–1 in the first round of the League Cup. Holmes started Southampton's opening seven games of the season, and scored a second goal, once again in the League Cup, but was injured in a 4–1 defeat to Queens Park Rangers in September. Holmes left Rangers' ground on crutches after suffering medial ligament damage in his right knee. The injury forced him to spend six weeks in a leg brace, and kept him out of action for three months. Although it did not require surgery, Holmes also suffered some cartilage damage, which had to be treated by a minor operation.