Crude extracts of Lychnophora pohlii were tested in vitro against trypomastigote forms of Trypanosoma cruzi, and the dichloromethane and methanol crude extracts from leaves plus inflorescences were found to have trypanocidal activity. The bioassay-guided fractionation of the extracts yielded seven active compounds: the sesquiterpene lactones lychnopholide, centratherin, goyazensolide and 15-desoxygoyazensolide in the dichloromethane extract, and caffeic acid and the flavonoids luteolin and vicenin-2 in the methanol extract. One active caffeoyl quinic acid derivative was isolated from the inactive hydroalcoholic extract of leaves plus inflorescences. Chemically, the plant has sesquiterpene lactone type furanoheliangolides, flavonoids, caffeic acid, a caffeoyl quinic acid derivative, which are characteristic of the Vernonieae.