Introduction: Although hypothermia is independently associated with an increased mortality in trauma patients, it might be an effective therapeutic approach for otherwise lethal hemorrhage. The effect of hypothermia on microcirculation, however, has been poorly studied in this setting. Our goal was to characterize the effects of hypothermia on microcirculation in normal conditions and in severe hemorrhagic shock. Methods: In anesthetized and mechanically ventilated sheep, we measured cardiac output (CO), renal blood flow (RBF), and systemic and renal O 2 consumption (VO 2 ). Cortical renal, intestinal villi, and sublingual microcirculation was assessed by IDF-videomicroscopy. After basal measurements, sheep were assigned to hypothermia (n ¼ 12) and normothermia (n ¼ 12) groups. Central temperature was reduced to $348C and maintained at baseline in each group, respectively. Measurements were repeated after 1 h of hemodynamic stable conditions and 1 h of severe hemorrhagic shock. Results: In conditions of hemodynamic stability, the hypothermia group showed lower CO, RBF, and systemic and renal VO 2 than the normothermia group. Red blood cell velocity was also lower in renal, villi, and sublingual microvascular beds (836 AE 195 vs. 1,066 AE 162, 916 AE 105 vs. 1051 AE 41, and 970 AE 182 vs. 1,102 AE 49 mm/s, respectively; P < 0.0001 for all). In hemorrhagic shock, most of the microvascular variables were similarly compromised in both the groups. In hypo-and normothermia groups, the percentage of reduction in perfused vascular density was higher in renal than in intestinal and sublingual microcirculation (66 AE 31 vs. 31 AE 23 and 15 AE 15%, and 78 AE 26 vs. 32 AE 37 and 18 AE 21%, P < 0.01 for both). Conclusions: This is the first experimental study assessing the effect of systemic hypothermia on microcirculation in severe hemorrhagic shock. The main finding was that hypothermia did not hamper additionally the microcirculatory derangements induced by hemorrhagic shock. In addition, renal microcirculation was more susceptible to hemorrhagic shock than villi and sublingual microcirculation.