From the aerial parts of Achillea setacea W. & K. (Asteraceae) the main sesquiterpenes were isolated. Their structures were determined by means of 2D-NMR and MS as 11,13-dehydrodeacetylmatricarin (1) (= 14-deoxylactucin), rupicolin A (2), and rupicolin B (3). These are the first compounds with an alpha-methylene-gamma-lactone structure isolated from a species belonging to the Achillea millefolium aggregate. Achillicin, achillin, 8-hydroxyachillin, 8-acetoxyachillin, and matricin could not be detected in A. setacea. For both rupicolin B and 11,13-dehydrodeacetylmatricarin an anti-inflammatory activity was found in the croton oil ear test.