Abstract One new highly degraded steroid, namely 21‐nor‐4‐ene‐chaxine A ( 1 ) furnishing a 5/6/5‐tricyclic, along with one known related analogue ( 2 ), were isolated from the South China Sea sponge Spongia officinalis . Their structures including absolute configurations were established by extensive spectroscopic data analysis, TDDFT‐ECD calculation, and comparison with the spectral data previously reported in the literature. Compound 1 represent the new member of incisterols family with a highly degradation in ring B. In vitro bioassays revealed compound 2 exhibited significant anti‐microglial inflammatory effect on lipopolysaccharide (LPS)‐induced inflammation in BV‐2 microglial cells.