Chemical investigation of the EtOAc extracts of marine-derived fungal isolates Aspergillus sp. SF-5974 and Aspergillus sp. SF-5976 yielded a new dihydroisocoumarin derivative (1) and 12 known metabolites. The structures of the isolated metabolites were established by extensive spectroscopic analyses, including 1D and 2D NMR spectra and MS data. Among the metabolites, the absolute configuration of 5'-hydroxyasperentin (6) was determined by single-crystal X-ray diffraction analysis. The in vitro antineuroinflammatory effects of the metabolites were also evaluated in lipopolysaccharide (LPS)-stimulated microglial cells. Among the isolated metabolites, dihydroisocoumarin derivatives 1-6 (10-80 μM) were shown to inhibit LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, in LPS-stimulated BV2 microglia. Further, 1 (20-80 μM) was found to suppress the phosphorylation of the inhibitor of nuclear factor kappa B-α (IκB-α), interrupt the nuclear translocation of nuclear factor kappa B (NF-κB), and decrease the activation of p38 mitogen-activated protein kinase (MAPK).