New noninvasive methods for monitoring cerebrovascular pressure reactivity coupled with a blood-based assay for brain-specific injury in preterm infants could allow early diagnosis of brain injury and set the stage for improved timing and effectiveness of interventions. Using an adaptation of near-infrared spectroscopy, we report a case of a very low birth weight infant undergoing hemoglobin volume index monitoring as a measure of cerebrovascular pressure reactivity. During the monitoring period, this infant demonstrated significant disturbances in cerebrovascular pressure reactivity that coincided with elevation of serum glial fibrillary acidic protein and new findings of brain injury on head ultrasound. This case report demonstrates the potential of emerging noninvasive monitoring methods to assist in both detection and therapeutic management to improve neurologic outcomes of the very low birth weight neonate.