Microbial products have contributed to human health care and the treatment of diseases. Fungi isolated from marine environments are a rich source of bioactive natural products as well as terrestrial isolates, and a large number of metabolites with unique structures and bioactivities have been reported from marine-derived fungi. During the course of an antifungal screening assay, we found that marine-derived Penicillium copticola strain TPU1270 isolated from Iriomote Island in Okinawa, Japan, exhibited growth inhibitory activity against Mucor hiemalis IAM6088 (20 mm at 200 μg per disc). Bioassay-guided isolation from the culture broth of strain TPU1270 yielded an open-chain hemisuccinimide, named penicillimide (1), together with five known eremophilane sesquiterpenes: sporogen-AO 1 (2), 3-acetyl-13-deoxyphomenone (3), 6-dehydropetasol (4), 7-hydroxypetasol (5), and petasol (6) (Figure 1a). Compound 1 has been obtained by organic synthesis, and this is the first time to report this compound as a natural product. The isolation and antifungal activities of compounds 1–6 have been described herein.