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The effects of RBC transfusion on microvascular perfusion are not well documented. We investigated the effect of RBC transfusion on sublingual microcirculation in hemorrhagic shock patients.Prospective, preliminary observational study.A 28-bed, surgical ICU in a university hospital.Fifteen hemorrhagic shock patients requiring RBC transfusion.Transfusion of one unit of RBCs.The sublingual microcirculation was assessed with a Sidestream Dark Field imaging device before and after RBC transfusion. After transfusion of one unit of RBC, hemoglobin concentration increased from 8.5 g/dL (7.6–9.5 g/dL) to 9.6 g/dL (9.1–10.3 g/dL) g/dL (p = 0.02) but no effect on macrocirculatory parameters (arterial pressure, cardiac index, heart rate, and pulse pressure variations) was observed. Transfusion of RBC significantly increased microcirculatory flow index (from 2.3 [1.6–2.5] to 2.7 [2.6–2.9]; p < 0.003), the proportion of perfused vessels (from 79% [57–88%] to 92% [88–97%]; p < 0.004), and the functional capillary density (from 21 [19–22] to 24 [22–26] mm/mm2; p = 0.003). Transfusion of RBC significantly decreased the flow heterogeneity index (from 0.51 [0.34–0.62] to 0.16 [0.04–0.29]; p < 0.001). No correlations were observed between other macrovascular parameters and microvascular changes after transfusion. The change in microvascular perfusion after transfusion correlated negatively with baseline microvascular perfusion.RBC transfusion improves sublingual microcirculation independently of macrocirculation and the hemoglobin level in hemorrhagic shock patients. The change in microvascular perfusion after transfusion correlated negatively with baseline microvascular perfusion. Evaluation of microcirculation perfusion is critical for optimization of microvascular perfusion and to define which patients can benefit from RBC transfusion during cardiovascular resuscitation.