Before the 2005 season, the Boston Red Sox agreed to a minor league contract with Petagine. He underwent knee surgery in spring training, preventing him from making the 25-man roster. In August, first baseman John Olerud was placed on the 15-day disabled list and his roster spot was filled by Petagine, who'd had a productive Triple-A season (including a .327 batting average with 20 home runs and 69 RBI in 74 games at Pawtucket). In 18 games with Boston, he hit .281 (9-for-34) with one home run and nine RBI.