Background: Energy drinks, such as Red Bull (RB), have become very popular, especially among young adults, who believe that they provide more energy and improve performance levels. Endocrine glands such as the pituitary and adrenal glands (which are functionally connected through the pituitary-adrenal axis), are among the organs susceptible to the cytotoxic effects of Red Bull. Therefore, the goal of the present study was to assess the effects of RB chronic intake on these two glands in adult male albino rats as well as the consequences of its withdrawal. Methods: Thirty-nine adult male albino rats were equally divided into 3 groups:control group (I), Red Bull group (II), and withdrawal group (III). Specimens from both glands were processed for light and electron microscopic examination. Analysis of serum levels of ACTH and corticosterone and morphometric and statistical analyses were also done. Results: The Red Bull-given group displayed significantly lower serum levels of ACTH and corticosterone in comparison to the control group. Both the anterior lobe of the pituitary and the adrenal cortex showed marked degenerative changes (dark nuclei and vacuolated cytoplasm) with decreased percentage of pituitary basophils, increased zona faciculata thickness with marked fibrosis. Immunohistochemical staining for anti- iNOS and anti-Caspase 3 showed significant increase compared to the control group. Cessation of RB intake showed partial improvement in the histopathological and biochemical changes in both glands. Conclusions: Chronic intake of energy drinks alters the pituitary-adrenal axis structure and function, which cannot be completely ameliorated by cessation of its administration.