Noninvasive measurement of cerebral venous oxygenation in neonates could provide critical information for clinicians such as cerebral hypoxia without the risks involved with invasive catheterization. Evaluation of cerebral hypoxia is important in many clinical settings such as hypoxic-ischemic encephalopathy, perfusion monitoring in cardiovascular surgery or in traumatic brain injury. By probing the superior sagittal sinus (SSS), a large central cerebral vein, we can obtain stable signals with our recently developed multi-wavelength, fiber-coupled laser diode optoacoustic system for measurement of SSS blood oxygenation. The neonatal SSS oxygenation was measured in the reflection mode through open anterior and posterior fontanelles without obscuration by the overlying calvarium. In the transmission mode it was measured through the skull in the occipital area. Our device is lightweight, easily maneuverable, and user friendly for physicians. We monitored the SSS oxygenation in neonates admitted to the Neonatal Intensive Care Unit (NICU) of UTMB with varying gestation, birth weight and clinical histories to identify normal range and difference between neonates with and without risk factors for cerebral hypoxia.