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Hyperkalemia is a known adverse effect of trimethoprim-sulfamethoxazole, usually occurring at high doses. However, fatal hyperkalemia at low doses has rarely been reported. We present the case of an 80-year-old Japanese woman who experienced a cardiac arrest due to severe hyperkalemia after starting low-dose trimethoprim-sulfamethoxazole. This case suggests that trimethoprim-sulfamethoxazole can cause severe hyperkalemia and sudden death, even at low doses. When trimethoprim-sulfamethoxazole is administered, even at low doses, periodic monitoring of electrolyte levels is necessary, with the interval depending on concomitant medications and renal function.