Replacement of invasive monitoring of cerebral venous oxygenation with noninvasive techniques offers great promise in the management of life-threatening neurologic illnesses including traumatic brain injury. We developed and built an optoacoustic system to noninvasively monitor cerebral venous oxygenation; the system includes a nanosecond Nd:YAG laser and a specially designed optoacoustic probe. We tested the system in vitro in sheep blood with experimentally varied oxygenation. Our results demonstrated that (1) the amplitude and temporal profile of the optoacoustic waves increase with blood oxygenation in the range from 24% to 92%, (2) optoacoustic signals can be detected despite optical and acoustic attenuation by thick bone, and (3) the system is capable of real-time and continuous measurements. These results suggest that the optoacoustic technique is technically feasible for continuous, noninvasive monitoring of cerebral venous oxygenation.