Although Plasmodium falciparum malaria and Q fever are both prevalent in Africa, there have been no reports of co-infection to date. We report a case who returned from the Comoros archipelago diagnosed by serologic analysis as well as detection of Coxiella burnetii DNA in acute-phase serum. Thus, Q fever may be associated with malaria infection in travelers returning from disease-endemic countries. This diagnosis should be considered when the response to malaria treatment is incomplete.