Cytosporolides A-C (1-3), three caryophyllene-derived meroterpenoids with a unique peroxylactone skeleton, were isolated from cultures of the fungus Cytospora sp. Their structures were elucidated by NMR spectroscopy, and the absolute configuration of the 5,6-diol moiety in 1 was assigned using Snatzke's method. Compounds 1-3 showed significant antimicrobial activity against the Gram-positive bacteria Staphylococcus aureus and Streptococcus pneumoniae.