Four new polyoxygenated briarane-type diterpenoids, briaexcavatolides O-R (1-4), have been isolated from a gorgonian octocoral Briareum excavatum. Their structures were determined using spectroscopic and chemical methods. Metabolites 1-3 were found to contain oxygenated substituents at C-2, C-3, and C-4, and the relative configurations were assigned as 2R*,3R*,4R* at these three positions. Briaranes containing this type of stereochemistry are reported for the first time. The structures of metabolites 1 and 2 were further confirmed by single-crystal X-ray analyses. Compound 2 has been shown to exhibit significant cytotoxicity toward P-388 and HT-29 cancer cells.