BACKGROUND Methemoglobinemia due to the administration of sulfamethoxazole/trimethoprim has been documented in a series of case reports. However, all of these reports are on adult patients, and all patients received at least daily administration of sulfamethoxazole/trimethoprim for the treatment of active or suspected infection. CASE REPORT Herein we report the development of methemoglobinemia in a pediatric patient receiving sulfamethoxazole/trimethoprim three times weekly for the prophylaxis of opportunistic infections. CONCLUSIONS The clinician should always consider sulfamethoxazole/trimethoprim, even when administered for opportunistic infection prophylaxis at reduced doses and intervals, as a possible cause of methemoglobinemia.