A 32-year-old man presented with a 2-month history of fever and pancytopenia. Based on the clinical examination, we diagnosed him with human immunodeficiency virus (HIV) infection and Pneumocystis jirovecii pneumonia (PCP). A few days after receiving oral trimethoprim-sulfamethoxazole (TMP-SMX), his fever and pancytopenia worsened. Suspecting drug-induced pancytopenia, we discontinued TMP-SMX; however, his condition did not improve. We observed a marked increase in his blood ferritin levels and hemophagocytosis on bone marrow aspiration. Therefore, we diagnosed the patient with hemophagocytic syndrome (HPS). We restarted TMP-SMX and added antiretroviral drugs (emtricitabine, dolutegravir, and tenofovir) and high-dose corticosteroids to the regimen. Eventually, the fever, pancytopenia, and pulmonary opacities disappeared. Pulmonologists often treat PCP patients, and high rates of hospital mortality are reported in HPS patients who have HIV infection or pulmonary involvement. If cytopenia occurs in a PCP patient after TMP-SMX administration, we recommend that HPS be considered a cause of drug-induced cytopenia.