We assessed the ability of a normalized autonomic nervous system (ANS) stress measure defined as an increase in the percentage of pulse rate from a baseline homeostasis state to identify corresponding changes in circulating blood volume to quantitatively recognize hypovolemia and predict subsequent autoregulatory exhaustion. Autoregulatory exhaustion is defined as the point where decreased circulatory volume exceeds the compensatory mechanism capacity to maintain flow and pressure. We derived frequency-based measures of pulse rate and pulse strength using a reflective pulse oximeter waveform of a photoplethysmograph placed on the forehead. This study was performed at the Penn State Heart and Vascular Institute, Hershey, Pennsylvania, in June 2010. Ten healthy subjects (5 each male and female) were placed supine in a lower-body negative-pressure chamber to induce central volume loss. Systolic blood pressure was continuously measured, and a value of less than 90 mm Hg defined autoregulatory exhaustion. Derived measures of circulating blood volume were compared with echocardiographic measures to access photoplethysmograph-derived circulatory volume measure relative to traditional cardiac hemodynamics. All 10 subjects produced consistent patterns of response characterized as a progressively increasing ANS stress in response to increasing lower-body negative pressure. Three subjects exhibited autoregulatory exhaustion, and ANS stress increased markedly on the step before displaying hypotension in these subjects but not the others. Results demonstrate the potential to use model-based measures to serve as a definitive presymptom predictive tool to recognize an impending hypovolemic condition, making this approach suitable for chronic care or for the management of hemodialysis patient where resting baseline measures can be obtained.