|| May 21 || @ Red Sox || 6 – 3 || Colón (1-0) || Tomko (2-5) || || 37,674 || 21-25 |- bgcolor="ffbbbb" | 47 || May 22 || @ Red Sox || 11 – 8 || Matsuzaka (8–0) || Bannister (4–6) || Papelbon (14) || 37,613 || 21-26 |- bgcolor="ffbbbb" | 48 || May 23 || @ Blue Jays || 7 – 1 || Halladay (5-5) || Greinke (5-2) || || 24,207 || 21-27 |- bgcolor="ffbbbb" | 49 || May 24 || @ Blue Jays || 6 – 0 || Litsch (6-1) || Hochevar (3-4) || || 28,162 || 21-28 |- bgcolor="ffbbbb" | 50 || May 25 || @ Blue Jays || 3 – 1 || McGowan (3-4) || Meche (3-7) || Ryan (11) || 29,315 || 21-29 |- bgcolor="ffbbbb" | 51 || May 26 || @ Blue Jays || 7 – 2 || Marcum (5-3) || Tomko (2-6) || || 23,157 || 21-30 |- bgcolor="ffbbbb" | 52 || May 27 || Twins || 4 – 3 (12) || Crain (2-2) || Núñez (3-1) || Guerrier (1) || 17,191 || 21-31 |- bgcolor="ffbbbb" | 53 || May 28 || Twins || 9 – 8 (10) || Crain (3-2) || Peralta (0-2) || Nathan (14) || 13,621 || 21-32 |- bgcolor="ffbbbb" | 54 || May 29 || Twins || 5 – 1 || Slowey (2-4) || Hochevar (3-5) || || 12,336 || 21-33 |- bgcolor="ffbbbb" | 55 || May 30 || Indians || 5 – 4 || Lee (8-1) || Tomko (2-7) || Borowski (4) || 25,243 || 21-34 |- bgcolor="bbffbb" | 56 || May 31 || Indians || 4 – 2 || Davies (1-0) || Sabathia (3-7) || Soria (12) || 23,923 || 22-34 |- |- bgcolor="bbffbb" | 57 || June 1 || Indians || 6 – 1 || Bannister (5-6) || Byrd (2-5) || || 22,345 || 23-34 |- bgcolor="ffbbbb" | 58 || June 3 || @ White Sox || 9 – 5 || Floyd (6-3) || Greinke (5-3) || || 21,727 || 23-35 |- bgcolor="ffbbbb" | 59 || June 4 || @ White Sox || 6 – 4 (15) || Dotel (3-2) || Gobble (0-1) || || 23,515 || 23-36 |- bgcolor="ffbbbb" | 60 || June 5 || @ White Sox || 6 – 2 || Contreras (6-3) || Meche (3-8) || || 25,104 || 23-37 |- bgcolor="bbffbb" | 61 || June 6 || @ Yankees