Croton cajucara Benth. is a medicinal plant popularly used in the Brazilian Amazonia, where it is known as sacaca, being consumed as tea, decoction or infusion of the leaves and stem bark. From a decoction of the leaves, a comprehensive phytochemical analysis was developed by liquid chromatography-mass spectrometry. Many compounds were identified for the first time in C. cajucara, such as O-glycosides of kaempferol and quercetin, flavonoid-C-glycosides, tannins and cinnamic acid derivatives. These compounds were fractionated by polarity and assayed for their anti-inflammatory activity, using a model of mice edema, induced by an intraplantar injection of carrageenan. All fractions exhibited anti-inflammatory properties.