BACKGROUND: Hypoxic ischemia (HI) is one of the common causes of neonatal brain injury, leading to neurodevelopmental disorders such as cerebral palsy, epilepsy, and cognitive deficits. In this study, we evaluated neuroprotective effects of vitamin C on the neonatal HI brain injury mouse model. METHODS: Brain damage measurement, sensorimotor function in the neonatal period, learning and memory ability in adulthood were carried out in mice treated with vitamin C daily for 7 consecutive days following HI brain injury at postnatal day 7. RESULTS: Vitamin C treatment significantly reduced the hippocampus damage area, infarction volume, hippocampal neuron loss, and suppressed the neuroinflammation after HI injury. Additionally, it improved performance on neonatal sensorimotor function tests and learning and memory ability in adulthood. CONCLUSIONS: Vitamin C reduced brain injury and improved functional recovery in the neonatal hypoxic ischemia brain damage (HIBD) model. IMPACT: Vitamin C treatment significantly reduced neuron loss and suppressed the neuroinflammation after hypoxic-ischemic brain injury. Vitamin C treatment enhanced sensorimotor functions in neonates and improved cognitive abilities in adults after hypoxic-ischemic brain injury. Vitamin C could be an attractive candidate drug in clinical trials of hypoxic-ischemic encephalopathy therapy.