BACKGROUND: Pure red cell aplasia (PRCA) is a rare cause of anemia characterized by decreased red blood cell production, often associated with thymomas. While thymectomy is commonly performed to treat thymoma-associated PRCA, the development of PRCA post-thymectomy is less understood. CASE PRESENTATION: We present a case of a 25-year-old woman who developed PRCA and autoimmune diabetes mellitus (DM) following radical thymectomy for malignant thymoma. Initial treatment with prednisolone showed minimal improvement, leading to the inclusion of rituximab. This combination resulted in a significant increase in reticulocyte counts and transfusion independence. DISCUSSION: This case highlights the potential for PRCA to develop after thymectomy and the challenges of treating PRCA in the context of additional conditions like autoimmune DM. While immunosuppressive therapies such as cyclosporin A and corticosteroids are standard, their side effects necessitated exploring alternative treatments. Rituximab proved effective and was well-tolerated, suggesting its potential as a primary option in similar cases. CONCLUSION: This case illustrates the occurrence of PRCA after thymectomy and highlights rituximab's effectiveness as a treatment option, offering a viable alternative to standard therapies in managing this complex condition.