CONTEXT: Near infrared spectroscopy (NIRS) is a noninvasive tool for assessing local oxygen balance. In circulatory shock, the microcirculatory environment as measured by NIRS during resuscitation may provide additional diagnostic tools of value to the critical care physician. HYPOTHESIS: To assess whether a relative increase in peripheral NIRS was correlated with a clinically relevant increase in cardiac output following a fluid bolus in a swine model of shock. METHODS AND MODELS: Nine healthy young adult swine with median weight 80 kg (interquartile range, 75-83 kg) were anesthetized and surgically instrumented. They underwent a controlled hemorrhage of 20% of their blood volume followed by partial or complete aortic occlusion to create a variable ischemia-reperfusion injury. Next, the animals underwent four 500-mL plasmalyte boluses over 9 minutes each followed by a 6-minute pause. The animal then underwent a 25% mixed auto/homologous blood transfusion followed by four more 500 mL plasmalyte boluses over 9 minutes. Finally, the animals underwent a 25% mixed auto/homologous blood transfusion followed by an additional four rounds of 500-mL plasmalyte boluses over 9 minutes. Left thoracic limb NIRS, descending thoracic aortic flow (dAF), arterial blood pressure (MAP), central venous pressure (CVP), and mixed central venous oxygen saturation (Svo2) were measured continuously for comparison. RESULTS: The area under the receiver operating curve for an increase in dAF of 10% in response to a 500 mL bolus based on a percent increase in the proximal NIRS was 0.82 with 95% CI, 0.72-0.91; Svo2, 0.86 with 95% CI, 0.78-0.95; MAP, 0.75 with 95% CI, 0.65-0.85 and CVP, 0.64 with 95% CI, 0.53-0.76. INTERPRETATION AND CONCLUSIONS: A dynamic relative increase in NIRS in response to a crystalloid challenge has moderate discriminatory power for cardiac output augmentation during shock in a swine model of ischemia-reperfusion injury. NIRS performed as well as invasive measurements (Svo2 and MAP) and better than CVP.