Two new metabolites, crassumolides H and I (2and 3), and crassumolide G (1) which was discovered for the first time from natural sources, were isolated from the ethyl acetate extract of a Taiwanese soft coral Lobophytum crassum, along with three known metabolites 4–6. The structures of metabolites 1–3were elucidated by extensive spectroscopic analysis and comparison of the NMR data with those of known compounds. Compounds 1–3were found to inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins at 10 µM in LPS-stimulated RAW264.7 marcophage cells.