We previously reported the neuroprotective potential of combined hydrogen (H) gas ventilation therapy and therapeutic hypothermia (TH) by assessing the short-term neurological outcomes and histological findings of 5-day neonatal hypoxic-ischemic (HI) encephalopathy piglets. However, the effects of H gas on cerebral circulation and oxygen metabolism and on prognosis were unknown. Here, we used near-infrared time-resolved spectroscopy to compare combined H gas ventilation and TH with TH alone. Piglets were divided into three groups: HI insult with normothermia (NT, n = 10), HI insult with hypothermia (TH, 33.5 ± 0.5 °C, n = 8), and HI insult with hypothermia plus H ventilation (TH + H, 2.1-2.7%, n = 8). H ventilation and TH were administered and the cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation (ScO) were recorded for 24 h after the insult. CBV was significantly higher at 24 h after the insult in the TH + H group than in the other groups. ScO was significantly lower throughout the 24 h after the insult in the TH + H group than in the NT group. In conclusion, combined H gas ventilation and TH increased CBV and decreased ScO, which may reflect elevated cerebral blood flow to meet greater oxygen demand for the surviving neurons, compared with TH alone.© 2023. The Author(s).