Circulatory shock may be fatal unless promptly recognized and treated. The most commonly used indicators of shock (hypotension and tachycardia) lack sensitivity and specificity. In the initial stages of shock, the body compensates by reducing blood flow to the peripheral (skin, muscle, etc.) circulation in order to preserve vital organ (brain, heart, liver) perfusion. Characteristically, this can be observed by a greater reduction in peripheral venous oxygenation (for instance, the axillary vein) compared to central venous oxygenation (the internal jugular vein). While invasive measurements of oxygenation are accurate, they lack practicality and are not without complications. We have developed a novel optoacoustic system that noninvasively determines oxygenation in specific veins. In order to test this application, we used lower body negative pressure (LBNP) system, which simulates hemorrhage by exerting a variable amount of suction on the lower body, thereby reducing the volume of blood available for central circulation. Restoration of normal blood flow occurs promptly upon cessation of LBNP. Using two optoacoustic probes, guided by ultrasound imaging, we simultaneously monitored oxygenation in the axillary and internal jugular veins (IJV). LBNP began at -20 mmHg, thereafter was reduced in a step-wise fashion (up to 30 min). The optoacoustically measured axillary oxygenation decreased with LBNP, whereas IJV oxygenation remained relatively constant. These results indicate that our optoacoustic system may provide safe and rapid measurement of peripheral and central venous oxygenation and diagnosis of shock with high specificity and sensitivity.