Emeriones A-C (1-3), three highly methylated polyketides with bicyclo[4.2.0]octene and 3,6-dioxabicyclo[3.1.0]hexane functionalities, were isolated from Emericella nidulans. An additional peroxide bridge in compound 3 led to the construction of an unexpected 7,8-dioxatricyclo[4.2.2.02,5]decene scaffold. The structures of 1-3 were elucidated by comprehensive spectroscopic techniques, and their absolute configurations were confirmed by single-crystal X-ray crystallographic analyses and ECD calculations. Compound 1 shows weak inhibitory effects on NO production in LPS-induced RAW264.7 cells.