Red Sox || 9–5 || Matsuzaka (3–3) || Pavano (2–4) || || 37,526 || 12–20 |- style="text-align:center; background:#fbb;" | 33 || May 9 || @ Red Sox || 2–1 || Okajima (1–0) || Hoey (0–1) || || 37,276 || 12–21 |- style="text-align:center; background:#fbb;" | 34 || May 10 || Tigers || 10–2 || Porcello (3–2) || Liriano (2–5) || || 38,949 || 12–22 |- style="text-align:center; background:#fbb;" | 35 || May 11 || Tigers || 9–7 || Benoit (1–2) || Capps (1–2) || Valverde (8) || 38,938 || 12–23 |- style="text-align:center; background:#fbb;" | 36 || May 13 || Blue Jays || 2–0 || Romero (3–4) || Burnett (0–2) || Francisco (3) || 38,809 || 12–24 |- style="text-align:center; background:#fbb;" | 37 || May 14 || Blue Jays || 9–3 (11) || Rauch (2–2) || Perkins (0–1) || || 39,934 || 12–25 |- style="text-align:center; background:#fbb;" | 38 || May 15 || Blue Jays || 11–3 || Morrow (2–2) || Duensing (2–3) || || 39,301 || 12–26 |- style="text-align:center; background:#fbb;" | 39 || May 16 || @ Mariners || 5–2 || Pineda (5–2) || Baker (2–3) || || 14,859 || 12–27 |- style="text-align:center; background:#bfb;" | 40 || May 17 || @ Mariners || 2–1 || Liriano (3–5) || Hernández (4–4) || Capps (6) || 16,015 || 13–27 |- style="text-align:center; background:#bfb;" | 41 || May 18 || @ Athletics || 4–3 (10) || Nathan (1–1) || Fuentes (1–4) || Capps (7) || 15,355 || 14–27 |- style="text-align:center; background:#bfb;" | 42 || May 19 || @ Athletics || 11–1 || Blackburn (3–4) || Ross (3–3) || || 22,320 || 15–27 |- style="text-align:center; background:#fbb;" | 43 || May 20 || @ Diamondbacks || 8–7 || Kennedy (5–1) || Duensing (2–4) || Paterson (1) || 27,450 || 15–28 |- style="text-align:center; background:#fbb;" | 44 || May 21 || @ Diamondbacks || 9–6 || Heilman (3–0) || Capps (1–3) || Putz (11) || 39,776 || 15–29 |- style="text-align:center; background:#fbb;" | 45 || May 22 || @ Diamondbacks || 3–2 || Hudson (5–5) || Burnett (0–3) || Putz (12) || 31,017 || 15–30 |- style="text-align:center; background:#fbb;" | 46 || May 23 || Mariners || 8–7 (10) || Wright (1–1) || Swarzak (0–2) || League (11) || 37,498 || 15–31 |- style="text-align:center; background:#bfb;" | 47 || May 24 || Mariners || 4–2 || Blackburn (4–4) || Fister (2–5) || || 37,691 || 16–31 |- style="text-align:center; background:#fbb;" | 48 || May 25 ||