Abstract: Eleven new highly oxygenated cembrane-type diterpenoids (1−7 and 10−13) and two known ones (8−9), were isolated from the South China Sea soft coral Sinularia pedunculata. Their structures were elucidated by extensive spectroscopic analysis, quantum mechanical-nuclear magnetic resonance (QM-NMR) approach and X-ray diffraction analysis. Among them, compounds 3 and 4 were rare cembrane diterpenoids that featured a tetrahydropyran moiety with 5,8-ether linkage and 4,8-ether linkage, respectively, while compounds 4 and 9 inhibited HBV DNA replication with IC₅₀ values of 0.87 and 1.15 μmol·L⁻¹ in HepAD38, respectively. Mechanism investigation suggested that compound 9 accelerated the formation of capsid, but did not affect the levels of HBV cccDNA, total RNA, and pgRNA.