Three new oxepin-containing natural products (1 ± 3) and two new fumiquinazoline metabolites (4 ± 5) have been isolated from organic extracts of the culture broth and mycelia of an Acremonium sp., a fungus obtained from the surface of the Caribbean tunicate Ecteinascidia turbinata. The structures of the five compounds were determined through extensive analysis of 1D- and 2D-NMR data, and mass spectrometry. Compound 1 exhibited good anti-inflammatory activity in a topical RTX-induced mouse ear edema assay. Compounds 4 and 5 exhibited weak antifungal activity toward Candida albicans in a broth microdilution assay.