An accurate method of estimating acute blood loss is essential in the evaluation of injured patients. Central venous oxygen (CVO2) saturation has been shown to be a sensitive and reliable correlate of blood loss in an animal model but its clinical validity is unproven. We evaluated 26 consecutive patients with an injury mechanism suggesting blood loss but who were deemed stable after initial evaluation. Vital signs (pulse, blood pressure, pulse pressure, urine output, CVP) and CVO2 saturation were serially measured. Blood loss was estimated by direct intracavitary collection or serial hematocrits and acute transfusion requirements. Despite stable vital signs, ten patients (39%) had CVO2 saturations under 65%. These patients had more serious injuries, significantly larger estimated blood losses, and required more transfusions than those patients with CVO2 saturation greater than 65%. Linear regression analysis demonstrated the superiority of CVO2 saturation to predict blood loss with a p value less than 0.005 relative to any of the normally followed parameters. CVO2 saturation is a reliable and sensitive method for detecting blood loss. It is a useful tool in the evaluation of acutely injured patients.