The ethanol extract of the aerial parts of A. elegantissima was fractionated by column and preparative thin-layer chromatography into six fractions (A-F) yielding 13 compounds, these were evaluated for their antitrypanosomal activity against T.b. brucei at different concentrations.Results: Thirteen compounds were isolated from A. elegantissima: (Z)-p-hydroxy cinnamic acid, stigmasterol, b-sitosterol, betulinic acid, bis-dracunculin, dracunculin, scopoletin, apigenin, dihydroluteolin, scoparol, nepetin, bonanzin, and 3 0 ,4 0 -dihydroxy bonanzin. The fractions D-F were found to be active at the concentration of 20 mg/ml and three compounds isolated from these fractions, scopoletin (MIC 0.19 mg/ml), 3 0 ,4 0 -dihydroxy bonanzin (MIC ¼ 6.25 mg/ml) and bonanzin (MIC ¼ 20 mg/ml), were found to be highly active. Discussion and conclusion: Artemisia elegantissima was phytochemically and biologically explored for its antitrypanosomal potential against T.b. brucei. The number and orientation of phenolic hydroxyl groups play an important role in the antitrypanosomal potential of coumarins and flavonoids. The compounds 3 0 ,4 0 -dihydroxy bonanzin and scopoletin with low MIC values, hold potential for use as antitrypanosomal drug leads.