Traumatic brain injury (TBI) and spinal cord injury are a major cause of death for individuals under 50 years of age. In the USA alone, 150,000 patients per year suffer moderate or severe TBI. Moreover, TBI is a major cause of combatrelated death. Monitoring of cerebral venous blood oxygenation is critically important for management of TBI patients because cerebral venous blood oxygenation below 50% results in death or severe neurologic complications. At present, there is no technique for noninvasive, accurate monitoring of this clinically important variable. We proposed to use optoacoustic technique for noninvasive monitoring of cerebral venous blood oxygenation by probing cerebral veins such as the superior sagittal sinus (SSS) and validated it in animal studies. In this work, we developed a novel, medical grade optoacoustic system for continuous, real-time cerebral venous blood oxygenation monitoring and tested it in human subjects at normal conditions and during hyperventilation to simulate changes that may occur in patients with TBI. We designed and built a highly-sensitive optoacoustic probe for SSS signal detection. Continuous measurements were performed in the near infrared spectral range and the SSS oxygenation absolute values were automatically calculated in real time using a special algorithm developed by our group. Continuous measurements performed at normal conditions and during hyperventilation demonstrated that hyperventilation resulted in approximately 12% decrease of cerebral venous blood oxygenation.