Marine sponges of the genus Plakortis have been a rich source of unique bioactive secondary metabolites such as polycyclic aromatic alkaloids or peroxy aliphatic acids and esters. We have also isolated plakorin, a cyclic peroxide with potent Ca2+-ATPase activating activity, and plakortenin, a cytotoxic carboxylic acid, from Okinawan Plakortis sponges. During our studies on bioactive substances from Okinawan marine organisms, we further investigated extracts of the sponges of the genus Plakortis and have isolated six novel fatty acid derivatives, manzamenones A-F (1-6) possessing a previously unknown carbon skeleton. This paper describes the isolation and structure elucidation of 1-6.