Phytochemical analysis of the ethyl acetate extract from the stem bark of Clusia pernambucensis G. Mariz, Clusiaceae, a Brazilian Cerrado species, led to the isolation and full characterization of a new xanthone, 1,7-dihydroxy-2-(3-methyl-2-butenyl)-6',6'-dimethylpyrano(2',3':3,4)xanthone, namely clusiaxanthone. Four previously unreported tocotrienols from this species were also isolated. A derivative was obtained from clusiaxanthone, 1-hydroxy,7-methoxy-2-(3-methyl2-butenyl)-6',6'-dimethylpyrano(2',3':3,4)xanthone (7-O-methylclusiaxanthone), and an additional derivative was obtained from Z- δ -tocotrienoloic acid. The structures of these compounds were established based on data from ¹H and 13C nuclear magnetic resonance (1D and 2D NMR), high resolution electrospray ionization mass spectrometry (HRESIMS) and infrared spectroscopy. The clusiaxanthone and its derivative were able to control macrophage infection by Leishmania (Leishmania) amazonensis amastigotes (IC50 = 66.9 and 57.4 µM, respectively). The cytotoxicity of the compounds was assessed in BALB/c mouse peritoneal macrophages.