A 34-year-old woman with HIV infection and no other opportunistic infections presented a classic sulfone syndrome, manifested by fever, rash, hemolytic anemia, and fulminant hepatitis due to dapsone hypersensitive reaction, with a fatal outcome. We believe this is the first reported fatal complication of dapsone in an HIV-infected patient. We to bring attention to this potentially fatal drug complication, which may become more common with widespread use of dapsone in HIV-infected patients. The package insert for dapsone recommends laboratory surveillance (hematologic and liver-related tests) during the first 4 to 6 weeks of therapy, and every 3 to 4 months thereafter. Our case report suggests that closer follow-up of patients receiving dapsone might be indicated.