Three new polychlorinated diketopiperazines, dysamides A [1], B [2], and C [3], and the known compound 2,3-dihydrodysamide C have been isolated from a marine sponge Dysidea fragilis collected off Hainan Island. Their structures were established by spectroscopic methods, and complete nmr assignments were made. The absolute configuration and conformation of dysamide A [1] were determined by X-ray crystallographic diffraction analysis. In this paper we report the isolation, structure elucidation, and absolute configuration determination of these compounds.