Two new eunicellin-based diterpenes, seco-briarellinone (1) and briarellin S (2), and a known seco-asbestinin (3) have been isolated from the methanolic extract of the common octocoral Briareum asbestinum collected in Bocas del Toro, Caribbean of Panama. The structures and relative stereochemistry of the compounds were defined using extensive spectroscopic analysis including 1D, 2D-nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). Compounds 1 and 2 displayed anti-inflammatory properties inhibiting nitric oxide (NO) production induced by lipopolisacharide (LPS) in macrophages with an Inhibitory concentration 50% (IC₅₀) of 4.7 μM and 20.3 μM, respectively. This is the first report of briarellin diterpenes containing a ketone group at C-12.