One uncommon sesquiterpenoid dimer (1), a new nardosinane-type sesquiterpenoid (3), along with two known sesquiterpenoids (2 and 4) were isolated from soft coral Litophyton nigrum using a structure-oriented HR-MS/MS approach. The configurations of the isolates were determined by spectroscopic data analyses, including HR-ESI-MS, 1D/2D NMR, single crystal X-ray diffraction, and DP4+ statistical analyses. Compound 3 exhibited potent PTP1B inhibitory activity (IC50 = 10.67 +/- 1.81 mu g/mL) compared to the positive control. (C) 2021 Elsevier Ltd. All rights reserved.