Storage time and residual leukocytes in red blood cell (RBC) units may be deleterious by increasing the accumulation of leukocyte-derived cytokines and by raising the adhesion of RBCs to endothelium. Leukodepleted RBC transfusion may reduce the incidence of infection and organ dysfunction. However, the influence of leukodepletion on microcirculation remains not well defined in ICU patients. In this context, an original study in a previous issue of Critical Care emphasizes the microcirculatory effects of transfusion of leukodepleted RBCs (post-storage leukoreduction) or nonleukodepleted RBCs in septic patients. This study suggests a positive rheological impact of leukodepleted RBCs in septic patients with an increase in sublingual microvascular flow and perfused vessel density. Given the variability in the microvascular response to RBC transfusion in individual patients, there is a need for monitoring the microcirculation to guide transfusion in patients with sepsis rather than deciding to transfuse RBCs according to an arbitrary hemoglobin level. Further studies to identify the microvascular response to RBC transfusion in ICU patients are warranted.