Sickle cell disease (SCD) is associated with the development of hypogonadism, but there is still controversy regarding its etiology and clinical implications. To evaluate the prevalence of hypogonadism in a population of men with SCD and characterize its etiology.We performed a cross-sectional study of 34 men with SCD aged > 18 years. Sociodemographic and clinical data, including anthropometric measurements (weight, height, and BMI), were obtained. Early morning blood samples were collected and total testosterone (TT), free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), a complete blood count, and hemoglobin electrophoresis were measured. Eugonadism was defined as T ≥ 300 ng/dL and LH ≤ 9.4 mUI/mL; primary hypogonadism as T < 300 ng/dL and LH > 9.4 mUI/mL; secondary hypogonadism as T < 300 ng/dL and LH ≤ 9.4 mUI/mL; and compensated hypogonadism as T ≥ 300 ng/dL and LH > 9.4 mUI/mL.Median age was 33 [26-41] years, and SS genotype was the most frequent (73.5%). The prevalence of eugonadism, compensated, and secondary hypogonadism was 67.5%, 26.4%, and 5.88%, respectively. No men with primary hypogonadism were identified in our sample. Those with compensated hypogonadism had also higher FSH levels (> 7.8 mUI/mL; p < 0.0001).In our study population of men with SCD a high prevalence of compensated hypogonadism was identified, which is a controversial and distinct clinical entity that warrants monitoring and further research.