Linezolid (LZD) is the first oxazolidinone with excellent safety and efficacy profiles against refractory infections caused by gram-positive organisms. Hematological toxicities such as thrombocytopenia, anemia, and leukocytopenia are common in LZD therapy; however, LZD-induced pure red cell aplasia (PRCA) is rare. An 83-year-old man diagnosed with pleural empyema caused by Staphylococcus aureus received LZD after developing resistance to multiple antibiotics. Although his infection-related symptoms were improved by LZD, progressive anemia was noticed after LZD therapy was initiated. Eight weeks after LZD administration began, his hemoglobin level was 5.7 g/dL and reticulocyte proportion was 0.36%, while his white blood cell and platelet counts remained unchanged since admission. Bone marrow examination revealed markedly decreased erythropoiesis with cytoplasmic vacuolation of erythroblasts. Anemia resolved by 14 days after cessation of LZD. It is important to increase the awareness among clinicians about the potential for the hematological effects associated with LZD, particularly for older patients with pre-existing anemia and treatment courses longer than 14 days. To detect bone marrow suppression, including PRCA, we suggest monitoring the complete blood count and reticulocyte count periodically in patients receiving long-term LZD therapy.