Hemorrhagic shock can be mitigated by timely and accurate resuscitation designed to restore adequate delivery of oxygen (DO2 ). Current doctrine of using systolic blood pressure (SBP) as a guide for resuscitation can be associated with increased morbidity. The compensatory reserve measurement (CRM) is a novel vital sign based on the recognition that the sum of all mechanisms that contribute to the compensatory response to hemorrhage reside in features of the arterial pulse waveform. CRM can be assessed continuously and non-invasively in real time. Compared to standard vital signs, CRM provides an early, as well as more sensitive and specific, indicator of patient hemorrhagic status since the activation of compensatory mechanisms occurs immediately at the onset of blood loss. Recent data obtained from our laboratory experiments on non-human primates have demonstrated that CRM is linearly related to DO2 during controlled progressive hemorrhage and subsequent whole blood resuscitation. We used this relationship to determine that the time of hemodynamic decompensation (i.e., CRM = 0%) is defined by a critical DO2 at approximately 5.3 mL O2 ∙kg-1 ∙min-1 . We also demonstrated that a target CRM of 35% during whole blood resuscitation only required replacement of 40% of the total blood volume loss to adequately sustain a DO2 more than 50% (i.e., 8.1 mL O2 ∙kg-1 ∙min-1 ) above critical DO2 (i.e., threshold for decompensated shock) while maintaining hypotensive resuscitation (i.e., SBP at ~90 mmHg). Consistent with our hypothesis, specific values of CRM can be used to accurately maintain DO2 thresholds above critical DO2 , avoiding the onset of hemorrhagic shock with whole blood resuscitation. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.