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Through our ongoing research on investigating new anti-inflammatory terpenoids derived from soft corals, seven capnellenes sourced from <i>Capnella imbricata</i> were discovered. Among these, three were previously unknown compounds named Δ⁹⁽¹²⁾-capnellene-6α,8β-diol (<b>1</b>), Δ⁹⁽¹²⁾-capnellene-6α,8β,10α-triol (<b>2</b>), and Δ⁹⁽¹²⁾-capnellene-2β,8β,10α-triol (<b>3</b>). The structures of all compounds were determined by spectroscopic analysis (IR, MS, 1D-, and 2D-NMR) and a comparison with the existing literature data. The compounds <b>1</b> and <b>2</b> were found to be the first-ever identified 6-hydroxy capnellenes. In the inflammation inhibitory assessments, compounds <b>1</b>–<b>7</b> were tested for their in vitro activities against inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in LPS-induced RAW264.7 cells. Capnellenes <b>2</b> and <b>5</b> demonstrated significant reductions in iNOS levels (27.73% and 47.61%) at a concentration of 10 μM. Additionally, capnellenes <b>1</b>, <b>5</b>, and <b>7</b> (at 10 μM) exhibited statistically significant inhibitions (ranging from 7.64% to 12.57%) against COX-2 protein expressions. Our findings indicated that the oxygen-bearing functionalities at C-8 and C-10 play critical roles in inhibiting iNOS protein induction, which can promote inflammation in LPS-induced RAW264.7 cells. Furthermore, a principal component analysis tool, the chemical global positioning system for natural products (ChemGPS-NP), was applied to confirm these capnellane-based sesquiterpenes as promising candidates for future anti-inflammatory agents targeting iNOS-related targets.