Two new cyclic peroxide-containing polyketide C16 acids 2 and 4 with their methyl esters 3 and 5 have been isolated from the Indo-Pacific marine sponge Plakortis aff. simplex. Both 2 and 3 are proposed to contain a single 1,2-dioxene ring, while 4 and 5 incorporate two 1,2-dioxene rings. The structures were elucidated mainly through 1D and 2D nmr spectral analysis. The methyl esters 3 and 5 were found to be active against cultured P-388 murine leukemia cells.