The Red Sox briefly held a 2-1 lead in the sixth inning Wednesday, but could not hold on, dropping a 3-2 decision to Oakland.
David Ortiz, however, was the man of the afternoon, clocking the 400th home run of his career in the fourth inning, a solo shot.
Brandon Inge had an RBI double in the sixth for Oakland and Jemile Weeks drove in the winning run for the A's, who swept the Red Sox in the three-game set.
Aaron Cook took the loss for Boston as he worked six innings and allowed three earned runs on nine hits.
The Red Sox will turn their attention to the division leading Yankees, who will play four games at Fenway Park starting Friday (double-header Saturday).