Lowell, who had surgery Dec. 30 to repair a torn ligament in his right thumb, played first base Monday in an 8-4 loss to the Baltimore Orioles. It was his first appearance at the position since 1998, when he played four games there for the New York Yankees' Triple-A affiliate.
Boston's offseason acquisition of third baseman Adrian Beltre will limit Lowell's time at the position he had manned for the Red Sox since 2006.
Luke Scott went 2 for 3 with four RBIs, including a three-run homer, for the Orioles.
Red Sox starter Tim Wakefield took the loss, allowing five runs and nine hits in 3 2/3 innings.