In this study we wanted to assess the relationship between mixed venous oxygen saturation (SVO2) and tissue oxygenation. For that, we compared the values of SVO2 with oxygen delivery (DO2), oxygen consumption (VO2), and markers of tissue hypoxia such as lactate and pyruvate during progressive hypoxemia. Eight 10-14-d-old piglets were anesthetized, tracheotomized, intubated, and ventilated. A fiberoptic catheter was placed in the carotid artery to monitor arterial oxygen saturation (SaO2). A thoracotomy was performed, and a fiberoptic catheter was placed in the pulmonary artery to monitor SVO2. A transit time ultrasound flow probe was positioned around the ascending aorta to measure aorta flow. Progressive graded hypoxemia was induced by decreasing fractional inspiratory oxygen concentration (FIO2) from 1.0 to 0.30, 0.21, 0.15, and 0.10. After each FIO2 interval blood samples were taken for blood gases, lactate, and pyruvate. DO2 and VO2 were calculated. SVO2 decreased similarly to SaO2. A value of SVO2 of more than 40% excluded oxygen restricted metabolism. When DO2 decreased below a critical range (8.4-12.8 mL/kg x min), SVO2 decreased below 15%, and lactate and the lactate/pyruvate ratio increased. We conclude 1) that baseline SVO2 values excluded oxygen-restricted metabolism, 2) that SVO2 values between 15 and 40% were not a marker for oxygen-restricted metabolism, and 3) that SVO2 values below 15% were associated with oxygen-restricted metabolism. Reduced SVO2 values must be interpreted as a change of the factors that determine the balance between DO2 and VO2 and as a warning that, with further reduction of SVO2, oxygen restricted metabolism can develop.