A detailed chemical research of soft coral Sarcophyton ehrenbergi from the South China Sea yielded five new cembranoids 1-5 featuring an α,β-unsaturated-γ-lactone moiety rarely at C-6 to C-19, along with one known related diterpene 6. The structures and absolute configurations of 1-5 were established in the light of extensive spectroscopic data analysis, chemical reaction, X-ray diffraction analysis, TDDFT/ECD (time-dependent density functional theory/electronic circular dichroism) calculations, and biosynthesis path. This study led to the stereostructural revision of 6, which was misassigned by erroneously applying the empirical ECD helicity rule, indicating a challenging and risky work to determine the structure of this type of marine cembranoids. In the TNF-α inhibitory biotest, compound 2 exhibited a potent inhibitory activity (IC50 = 8.5 μM), which was analogous to the positive control dexamethasone (IC50 = 8.7 μM).