Cerebral palsy is a leading cause of childhood physical disability, often resulting from neonatal hypoxic-ischemic brain injury. Reoxygenation and reperfusion following birth asphyxia can worsen brain damage, contributing to neurological impairments. While therapeutic hypothermia is the standard treatment for hypoxic-ischemic encephalopathy (HIE), no effective therapy exists to regenerate damaged neural tissue. In this study, 9-day-old mice underwent the right common carotid artery occlusion using an aneurysm clip. After exposure to hypoxia, reperfusion was induced by unclamping the artery, and then human cord blood mononuclear cells (hCBMC) were transplanted via the tail vein. Here we describe the procedure for inducing ischemia-reperfusion brain injury in mice and transplanting hCBMC. This model provides a controlled system for investigating the CBMC therapy in neonatal brain injury.