Lower body negative pressure (LBNP) creates a reversible hypovolemia by sequestrating blood volume in the lower extremities. This study sought to examine the impact of central hypovolemia on peripheral venous pressure (PVP) waveforms in spontaneously breathing subjects. With IRB approval, 11 healthy subjects underwent progressive LBNP (baseline, -30, -75, and -90 mmHg or until the subject became symptomatic). Each was monitored for heart rate (HR), finger arterial blood pressure (BP), a chest respiratory band and PVP waveforms which are generated from a transduced upper extremity intravenous site. The first subject was excluded from PVP analysis because of technical errors in collecting the venous pressure waveform. PVP waveforms were analyzed to determine venous pulse pressure, mean venous pressure, pulse width, maximum and minimum slope (time domain analysis) together with cardiac and respiratory modulations (frequency domain analysis). No changes of significance were found in the arterial BP values at -30 mmHg LBNP, while there were significant reductions in the PVP waveforms time domain parameters (except for 50% width of the respiration induced modulations) together with modulation of the PVP waveform at the cardiac frequency but not at the respiratory frequency. As the LBNP progressed, arterial systolic BP, mean BP and pulse pressure, PVP parameters and PVP cardiac modulation decreased significantly, while diastolic BP and HR increased significantly. Changes in hemodynamic and PVP waveform parameters reached a maximum during the symptomatic phase. During the recovery phase, there was a significant reduction in HR together with a significant increase in HR variability, mean PVP and PVP cardiac modulation. Thus, in response to mild hypovolemia induced by LBNP, changes in cardiac modulation and other PVP waveform parameters identified hypovolemia before detectable hemodynamic changes.