Monitoring of cerebral venous oxygenation is useful to facilitate management of patients with severe or moderate traumatic brain injury (TBI). Prompt recognition of low cerebral venous oxygenation is a key to avoiding secondary brain injury associated with brain hypoxia. In specialized clinical research centers, jugular venous bulb catheters have been used for cerebral venous oxygenation monitoring and have demonstrated that oxygen saturation < 50% (normal range is 55-75%) correlates with poor clinical outcome. We developed an optoacoustic technique for noninvasive monitoring of cerebral venous oxygenation. Recently, we designed and built a novel, medical grade optoacoustic system operating in the near-infrared spectral range for continuous, real-time oxygenation monitoring in the superior sagittal sinus (SSS), a large central cerebral vein. In this work, we designed and built a novel SSS optoacoustic probe and developed a new algorithm for SSS oxygenation measurement. The SSS signals were measured in healthy volunteers during voluntary hyperventilation, which induced changes in SSS oxygenation. Simultaneously, we measured exhaled carbon dioxide concentration (EtCO2) using capnography. Good temporal correlation between decreases in optoacoustically measured SSS oxygenation and decreases in EtCO2 was obtained. Decreases in EtCO2 from normal values (35-45 mmHg) to 20-25 mmHg resulted in SSS oxygenation decreases by 3-10%. Intersubject variability of the responses may relate to nonspecific brain activation associated with voluntary hyperventilation. The obtained data demonstrate the capability of the optoacoustic system to detect in real time minor changes in the SSS blood oxygenation.