The aim of the study was to investigate the morphological signs of hypoxic damage to the central nervous system (CNS) in premature infants. Material and methods: The autopsy reports of 20 premature infants were analyzed. The mean gestational age was 25.9±3.7 weeks, median birth weight was 650 [535;940] grams, and height was 32.6±5.4 cm. We analyzed clinical assessment of the infant's condition at birth, the course of the neonatal period, blood gases and acid-base status, the mode and parameters of mechanical lung ventilation, as well as the oxygenation index (OI) and oxygen saturation index (OSI). Macroscopic and histological signs of damage to various brain structures were studied during pathological anatomical examination. Cortex, parietal subcortex, hippocampus, striatum, cerebellum, foci of hemorrhage were examined. Results: The main causes of mortality in premature infants were severe asphyxia and its sequelae such as combined ischemic and hemorrhagic brain and spinal cord damage (45%). Severe hypoxia was confirmed by laboratory investigations. Critical lactate and acid-base blood values corresponding to decompensated lactate acidosis were registered in newborns including hyperlactatemia up to 9±3.6 mmol/l, pH 7.01±0.21, BE (-12.3) [-30; -7.9] mmol/l. The OI and OSI, indicating severity of hypoxia, were significantly elevated with their medians being 13.7[9.6;19.8] and 31.8[9.6;16.2], respectively. All infants had central nervous system lesions of varying severity with the underlying morphological immaturity. Pericellular and perivascular cerebral edema, unilateral or bilateral subcortical and subependymal hemorrhages, intraventricular hemorrhages of various degrees, up to tamponade and blood leakage into the cisterna magna, and cerebral leukomalacia were the most frequent findings. In all patients, altered neuronal shape and size as well as hyperchromic nuclei were revealed in the subcortical zone. Changes in all cell structures (cytoplasm, nuclei, and nucleoli), as well as satellitosis and neuronophagy, were characteristic. Conclusion: Polymorphic morphological changes were observed in the brain structures of premature infants who died as a result of perinatal hypoxia. Along with signs of morphological immaturity, irreversible changes in cortical and subcortical neurons were found. The magnitude of changes is associated with the severity of perinatal hypoxia and decompensated lactate acidosis.