Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity and mortality in newborns in both high- and low-income countries. The important determinants of its pathophysiology are neural cells and vascular components. In neonatal HIE, increased vascular permeability due to damage to the blood–brain barrier is associated with seizures and poor outcomes in both translational and clinical studies. In our previous studies, hydrogen gas (H2) improved the neurological outcome of HIE and ameliorated the cell death. In this study, we used albumin immunohistochemistry to assess if H2inhalation effectively reduced the cerebral vascular leakage. Of 33 piglets subjected to a hypoxic-ischemic insult, 26 piglets were ultimately analyzed. After the insult, the piglets were grouped into normothermia (NT), H2ventilation (H2), therapeutic hypothermia (TH), and H2combined with TH (H2-TH) groups. The ratio of albumin stained to unstained areas was analyzed and found to be lower in the H2group than in the other groups, although the difference was not statistically significant. In this study, H2therapy did not significantly improve albumin leakage despite the histological images suggesting signs of improvement. Further investigations are warranted to study the efficacy of H2gas for vascular leakage in neonatal HIE.