A 74-year-old woman was admitted to our hospital complaining of exertional dyspnea. She had started taking diaphenylsulfone for cutaneous small-vessel vasculitis seven months before admission and sulfamethoxazole/trimethoprim for prophylaxis against pneumocystis pneumonia four months before. She began to suffer from exertional dyspnea three months before admission. Laboratory tests, apart from SpO₂, and radiologic examinations revealed no abnormal findings. Compared with her PaO₂ on room air (81.5Torr), her SpO₂ was low, at 90%. Finally, after blood gas analysis with CO-oximetry revealed an elevated methemoglobin level, she was diagnosed with methemoglobinemia. Although the above two drugs were the suspected cause of the methemoglobinemia, only sulfamethoxazole/trimethoprim was discontinued because diaphenylsulfone was essential for treatment of the underlying disease. Seven months later, her methemoglobin level had decreased and her symptoms had improved. Up until now there have been no case reports of methemoglobinemia associated with the simultaneous administration of sulfamethoxazole/trimethoprim and diaphenylsulfone. Methemoglobinemia can develop with sulfamethoxazole/trimethoprim regardless of dose, dosage period, and patient age. Thus, it is necessary to consider methemoglobinemia in patients with dyspnea showing a dissociation between SpO₂ and PaO₂.