Hematologic complications represent a significant burden in individuals living with Human Immunodeficiency Virus (HIV) infection, with anemia being one of the most prevalent and clinically relevant manifestations. Central to the pathophysiology of HIV-associated anemia is the dysregulation of erythropoietin (EPO), the principal hormone governing red blood cell production. This review examines the intricate interplay between HIV infection and erythropoiesis, focusing on the mechanisms underlying EPO dynamics. Chronic inflammation, cytokine dysregulation, and direct viral effects disrupt the delicate balance of EPO regulation, leading to impaired erythropoiesis and anemia. Moreover, antiretroviral therapy (ART) may exert additional effects on EPO synthesis and hematopoiesis. Understanding these dynamics is crucial for devising effective therapeutic strategies tailored to individual patient needs. Future research endeavors should aim to unravel the complex pathways governing EPO regulation in HIV infection, paving the way for personalized management approaches aimed at alleviating anemia burden and improving patient outcomes.