Nine new polyoxygenated eremophilane sesquiterpenes, periconianones C-K (1-9), including one unusual isoeremophilane sesquiterpene, periconianone C (1), and four trinor-eremophilane sesquiterpenes, periconianones H-K (6-9), were isolated from the endophytic fungus Periconia sp. F-31. Compound 1 is the first furan-type isoeremophilane reported containing a linkage of C-8/C-11 and a 7,12-epoxy moiety. These compound structures, including absolute configurations, were elucidated through extensive spectroscopic data analysis, electronic circular dichroism, Mo2(AcO)4-induced circular dichroism, and single-crystal X-ray diffraction (Cu Kα). Compounds 2, 5, and 9 showed inhibition effects on lipopolysaccharide-induced NO production in BV2 cells by 10.2%, 18.3%, and 16.1% at a concentration of 1.0 μM, respectively, which is comparable to the positive control curcumin (12.9% at 1.0 μM).