The aim of this study was to evaluate the anti-inflammatory activities of the main constituents and epoxides derived from the essential oils (EOs) obtained from Tagetes lucida, Cymbopogon citratus, Lippia alba and Eucalyptus citriodora. The main constituents were isolated and then epoxidized with dimethyldioxirane (DMDO) in an acetone solution. The anti-inflammatory effects were studied in vitro on murine macrophages stimulated with bacterial lipopolysaccharide. All tested samples inhibited both nitric oxide (NO) and prostaglandin E2 (PGE2) production, but the EO from T. lucida and carvone exhibited the highest inhibitory effects. Most of the studied samples altered the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The studied epoxides inhibited both NO and PGE2 production, but at the RNA level, they primarily inhibited COX-2. These results show, for the first time, the anti-inflammatory effects of epoxides generated from the main components of EOs from Colombian plants.