A new chlorinated amino acid derivative with a rare 3-chloro-4-hydroxyphenyl unit named aspergamide A (1), along with three known compounds, xylarinol A (2), nectriapyrone (3), and asperisocoumarin A (4), were isolated from the sponge-derived fungus Aspergillus sp. LS53. Their structures were determined by combining detailed spectroscopic analysis and literature data. Compounds 1, 3, and 4 showed weak Vibrio harveyi inhibition with MIC values ranging from 16 to 64 μg/mL, whereas 2 was found to be inactive.