Leptospirosis has recently been described to cause concomitant infection with malaria. Only doxycycline has proven to have chemoprophylactic and therapeutic efficacy for both malaria and leptospirosis. To assess whether other traditional antimalarial agents have antileptospiral activity, we performed broth microdilution susceptibility testing of 16 Leptospira serovars (6 species/14 serogroups) to various agents. Artemisinin, atovaquone, chloroquine, mefloquine, primaquine, proguanil, pyrimethamine, sulfadoxine, quinine, quinidine, and combinations of atovaquone/proguanil and pyrimethamine/ sulfadoxine all had a 90% minimum inhibitory concentration (MIC90) > 25 μg/mL (the upper limit of testing). The only agents identified with the potential to treat both infections other than doxycycline (MIC90 = 1.56 μg/mL) were azithromycin (MIC90 = 0.02 μg/mL) and clindamycin (MIC90 = 0.2 μg/mL).