Administration of 2-deoxy-d-glucose (2-DG) attenuates sepsis-induced lactate and inflammatory cytokine production. Serum was harvested 8 hours after cecal ligation and puncture (CLP) sepsis. The levels of lactate (A), tumor necrosis factor (TNF-α; B), interleukin 1β (IL-1β; C), and interleukin 6 (IL-6; D) were analyzed with enzyme-linked immunosorbent assay. Administration of 2-DG at 0.25 or 1 g/kg body weight also significantly reduced serum lactate (E), TNF-α (F), and IL-1β (G). 2-DG (0.25 g/kg) attenuated sepsis-induced increases in the nuclear hypoxia-inducible factor (HIF-1α) levels (H). CLP sepsis did not significantly alter cytosolic HIF-1α levels in the myocardium (I). n = 4–6/group. *P < .05, **P < .01, and ***P < .001 compared with indicated groups.