Soft corals of the genus Sinularia have been proved to yield a wide variety of secondary metabolites. In order to search for novel bioactive substances from marine organisms, we have investigated the secondary metabolites of the soft corals Sinularia leptoclados and Sinularia sandensis. Chromatographic separation of the organic extracts of the Formosan soft coral Sinularia leptoclados, collected at Dongsha Atoll of the South China Sea, led to the isolation of four new steroids (1-3 and 11), along with an unexpected artificial sterol (5) and six known 9,11-secosteroids (4 and 6-10). In addition, the acetone extract of the soft coral, Sinularia sandensis, collected at the Tsau-Lou-Cho Island off the southwestern coast of Taiwan, yielded three novel sesquiterpenoids (12-14). The structures of the isolated metabolites were elucidated by extensive spectroscopic analyses (IR, UV, mass, optical rotations, CD, 1D and 2D NMR) and by comparison of the spectral data with those of the related known compounds. Moreover, the absolute configuration of 12 was established by application of modified Mosher¡¦s method. The cytotoxicity against of P-388 (mouse lymphocytic leukemia), HT-29 (human colon adenocarcinoma), and A-549 (human lung epithelial carcinoma) cells of metabolites 1-4 and 6-14 as well as the anti-HCMV (human cytomegalovirus) activities of metabolites 4, 10, 11, and 13 were evaluated. Metabolites 2, 4 and 6-10 exhibited significant activity against P-388 cell in vitro (IC50¡Ø4 mg/mL).