Chemical examination of an EtOAc extract of a cultured Acremonium sp. fungus from deep-sea sediments resulted in the isolation of 15 new eremophilane-type sesquiterpenoids, namely, acremeremophilanes A-O (1-15), together with seven known analogues. The structures of new compounds were determined through extensive spectroscopic analyses, in association with chemical conversions and ECD calculations for configurational assignments. The PKS-derived 4-hexenoic acid unit in 2-6 is rarely found in nature. All compounds were evaluated for inhibitory effects toward nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophage cells. Compounds 2-6 and 14 exhibited inhibitory effects with IC50 values ranging from 8 to 45 μM.