As a part of our ongoing interest in new bioactive compounds from natural sources, we studied Laurus nobilis (Lauraceae). This plant is widespread in the Mediterranean area and is used for medicinal and economic purposes. Chromatographic separations on active extracts led to the isolation of two new sesquiterpene lactones, 5a,9-dimethyl-3-methylene-3,3a,4,5,5a,6,7,8-octahydro-1-oxacyclopenta[c]azulen-2-one (1) and 3beta-chlorodehydrocostuslactone (2). The structures of the new compounds were identified by 1D and 2D NMR experiments, as well as high resolution mass spectrometry. The cytotoxic activity was also evaluated against three different tumor cell lines of human origin.