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Energy drinks are available worldwide and frequently consumed to increase energy level and compensate lack of sleep. Energy drinks consumers aim to improve their cognitive functions. Red Bull is the most popular energy drink consumed in Egypt. However, the link between the impact of energy drinks on the structure of hippocampal cornu ammonis 1 (CA1) and dentate gyrus (DG), a highly vulnerable brain regions to various insults, has not yet documented. To study the effect of energy drinks on structure of hippocampal CA1 and DG of adult male albino rats. Twenty one adult male albino rats were divided into three groups; group I control group, groups II and III received Red Bull, with a dose of 3.75 ml/kg/day orally using gastric tube for four and eight consecutive weeks respectively. At the end of the experiment, brains were dissected and hippocampal specimens were processed for histopathological and immunohistochemical studies. Histopathological examination of hippocampal sections in group II revealed vacuoles, decrease thickness of pyramidal cell layer with irregular dark or ghost nuclei. However, changes were more severe in group III with cracks in pyramidal cell layer, massive vacuolation and signet ring cells. Moreover, star shaped astrocytes and glial fibrillary acidic protein immuno-reactivity were more abundant in group III than in group II. Caffeinated energy drinks produced neurodegenerative changes and reactive astrocytosis in hippocampal CA1 and DG of adult male albino rats. These changes were duration-dependent being more severe in longer duration of intake.