Three new caffeic acid esters (1-3), four new lignans (4-7), and the known compounds (7′S)-parabenzlactone (8), dihydrocubebin (9), and justiflorinol (10) have been isolated from leaves of Piper sanguineispicum. Their structures were determined by spectroscopic methods, including 1D and 2D NMR, HRCIMS, CD experiments, and chemical methods. Compounds 1-10 were assessed for their antileishmanial potential against axenic amastigote forms of Leishmania amazonensis. Caffeic acid esters 1 and 3 exhibited the best antileishmanial activity (IC50 2.0 and 1.8 μM, respectively) with moderate cytotoxicity on murine macrophages. © 2010 The American Chemical Society and American Society of Pharmacognosy.