Objective:To examine the hypothesis that mixed venous oxygen saturation (S&OV0456;O2) values, which reflect the residual oxygen after tissue oxygen extraction, would be similar during hypoxic and anemic hypoxia.Design:S&OV0456;O2values, oxygen delivery, arterial oxygen content, and fractional oxygen extraction were compared, and critical values were determined based on lactate, the lactate/pyruvate ratio, and oxygen consumption during hypoxic and anemic hypoxia.Setting:Laboratory of physiology at a university hospital.Subjects:Two groups of eight piglets, 8 to 12 days old.Interventions:Piglets were anesthetized, tracheotomized, intubated, and ventilated. A thoracotomy was performed and a fiberoptic catheter was placed in the pulmonary artery to monitor S&OV0456;O2. A transit time ultrasound flow probe was positioned around the ascending aorta to measure aorta flow. Progressive hypoxic hypoxia was induced by decreasing FIO2from baseline (0.30-0.75) to 0.21, 0.15, and 0.10. Progressive anemic hypoxia was induced by a repeated isovolemic exchange transfusion with 50 mL of pasteurized plasma.Measurements and Main Results:Fifteen or 30 mins after each intervention, samples were taken from the carotid artery for blood gases, hemoglobin, lactate, and pyruvate and from the pulmonary artery for blood gases and hemoglobin. Hemodynamic, arterial oxygen saturation, and S&OV0456;O2measurements were made. The calculated oxygen delivery and oxygen consumption decreased in both hypoxic and anemic hypoxia. At the lowest oxygen delivery level of anemic hypoxia, the decrease in S&OV0456;O2was less than that in hypoxic hypoxia (−26% vs. −55%). The range of critical values for S&OV0456;O2calculated for each individual piglet below which lactate, the lactate/pyruvate ratio, and oxygen consumption rapidly changed from baseline value was significantly lower in hypoxic hypoxia (11% to 24%) than in anemic hypoxia (26% to 48%). Fractional oxygen extraction increased significantly but not with a change as high as in hypoxic hypoxia 0.31 (range, 0.20-0.41)vs.0.49 (range, 0.41-0.54).Conclusions:In comparison with hypoxic hypoxia, critical values of S&OV0456;O2are higher in anemic hypoxia, indicating that oxygen unloading from blood to tissues is impaired in anemic hypoxia. These characteristics in oxygen transport and capillary hemodynamics should be taken into consideration when S&OV0456;O2is used in clinical critical care.