The Red Sox, as the defending World Series champions, finished in second place in the American League East with a record of 95 wins and 67 losses, two games behind the Tampa Bay Rays.

In late March, the team started the regular season playing in Tokyo against the Oakland Athletics for MLB Japan Opening Day 2008.

In July, seven Red Sox players were selected for the AL All-Star team, with outfielder J. D. Drew being named the game's MVP.

On July 31, the Red Sox traded long-time star player Manny Ramirez to the Dodgers in a three-way blockbuster (which also included the Pirates) for Jason Bay and minor leaguer Josh Wilson.

In September, the team officially retired uniform number 6 in honor of Johnny Pesky.