Damages to the blood–brain barrier (BBB) and white matter (WM)/oligodendrocytes (OLs) are typical pathological findings in infants or animal models of neonatal hypoxia–ischemia (NHI). These injuries in turn produce severe neurological consequences, such as germinal matrix hemorrhage, periventricular leukomalacia, and cerebral palsy. Hence, the assessment of BBB and WM/OL damage, and its attenuation by experimental therapies, is an important component in the evaluation of NHI-induced brain injury. Immature brains have unique physiology and a different maturation status in the BBB and WM from the adult brain. Accordingly, there is a need of designing detection methodology tailored for the immature brain. This chapter describes several simple but reliable methods as well as some advanced imaging methods to assess the BBB and WM/OL damage following NHI. Specifically, we discuss sodium fluorescein-based assay of BBB permeability, zymography to evaluate matrix metalloproteinases, histological and immunocytochemical analysis of WM/OL injury, and magnetic resonance imaging-based quantification of gray-matter and WM injury.