One new alkaloid, named pyripyropene U (1), and six known natural products (2-7) were obtained from the marine sponge-derived fungus Aspergillus sp. SCSIO41420. Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses, while the absolute configurations of the new compound were unambiguously confirmed by theoretical electronic circular dichroism (ECD) calculation. Those natural products were evaluated in the antimicrobial tests against various fungi and bacteria, and 7 possessed obvious inhibitory activity against Staphylococcus aureus ATCC 29213.