['The microcirculation supplies oxygen (O2) and nutrients to all cells with the red blood cell (RBC) acting as both a deliverer and sensor of O2. In sepsis, a proinflammatory disease with microvascular complications, small blood vessel alterations are associated with multi-organ dysfunction and poor septic patient outcome. We hypothesized that microvascular autoregulation-existing at three levels: over the entire capillary network, within a capillary and within the erythrocyte-was impaired during onset of sepsis. This study had three objectives: 1) measure capillary response time within hypoxic capillaries, 2) test the null hypothesis that RBC O2-dependent adenosine triphosphate (ATP) efflux was not altered by sepsis and 3) develop a framework of a pathophysiological model.', 'This was an animal study, comparing sepsis with control, set in a university laboratory. Acute hypotensive sepsis was studied using cecal ligation and perforation (CLP) with a 6-hour end-point. Rat hindlimb skeletal muscle microcirculation was imaged, and capillary RBC supply rate (SR\u2009=\u2009RBC/s), RBC hemoglobin O2 saturation (SO2) and O2 supply rate (qO2\u2009=\u2009pLO2/s) were quantified. Arterial NOx (nitrite\u2009+\u2009nitrate) and RBC O2-dependent ATP efflux were measured using a nitric oxide (NO) analyzer and gas exchanger, respectively.', "Sepsis increased capillary stopped-flow (p\u2009=\u20090.001) and increased plasma lactate (p\u2009<\u20090.001). Increased plasma NOx (p\u2009<\u20090.001) was related to increased capillary RBC supply rate (p\u2009=\u20090.027). Analysis of 30-second SR-SO2-qO2 profiles revealed a shift towards decreased (p\u2009<\u20090.05) O2 supply rates in some capillaries. Moreover, we detected a three- to fourfold increase (p\u2009<\u20090.05) in capillary response time within hypoxic capillaries (capillary flow states where RBC SO2\u2009<\u200920\xa0%). Additionally, sepsis decreased the erythrocyte's ability to respond to hypoxic environments, as normalized RBC O2-dependent ATP efflux decreased by 62.5\xa0% (p\u2009<\u20090.001)."] Does sepsis impair microvascular autoregulation and delays capillary response within hypoxic capillaries?