In the course of a screening of Sudanese Asteraceae against protozoa causing tropical diseases, a crude DCM extract of Xanthium brasilicum Vell. was found highly active against Trypanosoma brucei rhodesiense (East African Sleeping Sickness, IC50 =0.1µg/mL). Bioactivity-guided fractionation yielded two monomeric and two dimeric xanthanolide sesquiterpene lactones (STL 1-4), all highly active. The unusual compound 5 was almost inactive as a pure compound. Compound 1 (8-epixanthatin) showed the lowest IC50 values against T. brucei and Leishmania donovani (visceral Leishmaniasis) of 0.34µM and 0.60µM, respectively. All compounds were reported as constituents of X. pungens [1] but no information on their bioactivity existed. Structure-activity studies with a variety of STL [2] are in progress.