Adequate resuscitation of patients from shock states depends on restoration of oxygen delivery (DO2) to tissues. Direct measurement of systemic DO2 during shock states requires invasive techniques such as pulmonary artery catheterization. These experiments were performed to examine the ability of near-infrared spectroscopy (NIRS), to measure regional tissue oxygenation in a large-animal model of hemorrhagic shock, and to compare these measures to global measures of oxygen delivery. Splenectomized female pigs (n = 11) were anesthetized, instrumented, and monitored. NIRS probes were placed on the leg, in the stomach via nasogastric tube, and on the liver during laparotomy. Hemorrhagic shock was induced by phlebotomy of 28% of blood volume. After 1 hour, resuscitation was with shed blood and crystalloid until cardiac output plateaued. Measurements of physiologic parameters, blood gases, lactate, intramucosal pH, and NIRS values for regional tissue hemoglobin oxygen saturation (StO2), and cytochrome a,a3 redox state were recorded at intervals throughout the experiment. Tissue oxygenation as measured by oxyhemoglobin saturation and cytochrome a,a3 redox (NIRS) correlated with measures of systemic DO2 throughout the experiment. The liver probe demonstrated blunted changes in tissue oxygenation suggesting relatively protected circulation. Intramucosal pH did not correlate well with DO2. Regional tissue oxygenation as measured by NIRS shows excellent correlation with global oxygen delivery. NIRS may allow estimation of systemic oxygen delivery using rapid non-invasive techniques.