Introduction. The functional activity of the pineal gland plays a dramatic important role in the adaptation topostnatal life and in the pathogenesis of the most common perinatal pathology of premature infants.The aim of the study. To determine the morphofunctional features of the pineal gland in premature infants withextremely low body weight.Material and methods. In 46 preterm infants with extremely low birth weight, the level of melatonin metabolite inurine 6-sulfoxymelatonin was determined at first day of life. The 20 dead infants underwent macro- and microscopicexamination of the pineal gland using the immunohistochemical method.Results. All preterm infants with extremely low birth weight had perinatal pathology, which led to death in 20 ofthem. Urinary excretion of the metabolite melatonin 6-sulfoximelatonin in preterm infants with extremely low birthweight in the first day of life, which had fatal consequences, significantly reduced compared with surviving children,indicating depletion of functional activity of the pineal gland and may be as a marker of adverse course of the neonatalperiod. Morphologically, in the pineal gland of premature infants with extremely low body weight there is an increasein morphofunctional activity of pineal cells. This is confirmed by morphometric data and increased expression ofMelanA and S100 in immunohistochemical studies. Macro- and microscopic data suggest that extrauterine existencein distress conditions accelerates the differentiation of the pineal gland (depletion) and indicates the presenceof damage to glandular tissue, which in turn reduces the synthesis of melatonin and its mediated metabolite 6 –sulfoxymelatonin in urine.Conclusions. Decreased urinary excretion of 6-sulfoximelatonin in preterm infants with extremely low birthweight in the first day of life and mophological changes in the pineal gland of deceased children indicate depletionof functional activity of the pineal gland in conditions of perinatal pathology