Epicoccins A-D (1-4), four unique epipolythiodioxopiperazines possessing unusual sulfur bridges, have been isolated from cultures of a Cordyceps-colonizing isolate of Epicoccum nigrum. The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data. The relative and absolute configuration of epicoccin A (1) was established by single-crystal X-ray diffraction analysis. Epicoccin A (1) showed modest antimicrobial activity.