Purpose: This study analyzes the semen parameters and gonadal hormone levels in infertile patients with sickle cell disease (SCD) and palpable varicoceles who underwent varicocelectomy for impaired semen parameters. Patients and methods: Improvements in the semen parameters—serum levels of total testosterone, follicle-stimulating hormone (FSH), and inhibin B—and testicular volume (TV) in 18 infertile patients with SCD were evaluated before and at 6 months after varicocelectomy. Results: Before varicocelectomy, all sperm parameters were affected, with high rates of low sperm concentration (83.3%), poor motility (88.9%), and abnormal morphology (77.8%). All sperm parameters were altered in 61.1%. On follow-up at 55.5 months after varicocelectomy, improvement in all the semen parameters was successful and complete in 22.2% but was not significant in 77.8%. The median follow-up period for sperm recovery was relatively long at 60.3 months. Total testosterone, FSH, and inhibin B were not significantly different before and after treatment (P > 0.05). However, testosterone, FSH, and TV significantly correlated with the semen parameters (P < 0.05). Moreover, a significant positive correlation was found between TV and inhibin B (P < 0.05), and the improvement in the semen parameters was significantly correlated with primary hypogonadism (P < 0.05). Conclusion: In adult men with SCD, varicocelectomy had a positive impact on the impaired seminal parameters and may be an option before sperm cryopreservation to improve future male fertility. Furthermore, primary testicular failure may be a feature of reversible spermatogenesis recovery in these patients.