Circulatory shock is a dangerous medical condition, in which blood flow cannot provide the necessary amount of oxygen to organs and tissues. Currently, its diagnosis and therapy decisions are based on hemodynamic parameters (heart rate, blood pressure, blood gases) and mental status of a patient, which all have low specificity. Measurement of mixed or central venous blood oxygenation via catheters is more reliable, but highly invasive and associated with complications. Our previous studies in healthy volunteers demonstrated that optoacoustic systems provide non-invasive measurement of blood oxygenation in specific vessels, including central veins. Here we report our first results of a clinical study in coronary artery bypass graft (CABG) surgery patients. We used a medical-grade OPO-based optoacoustic system developed in our laboratory to measure in real time blood oxygenation in the internal jugular vein (IJV) of these patients. A clinical ultrasound imaging system (GE Vivid e) was used for IJV localization. Catheters were placed in the IJV as part of routine care and blood samples taken via the catheters were processed with a CO-oximeter. The optoacoustic oxygenation data were compared to the CO-oximeter readings. Good correlation between the noninvasive and invasive measurements was obtained. The results of these studies suggest that the optoacoustic system can provide accurate, noninvasive measurements of central venous oxygenation that can be used for patients with circulatory shock.