A novel 19-membered cyclic depsipeptide, hedopeptolide (1), was isolated from Okeania sp., a marine cyanobacterium collected in Okinawa, Japan. Its gross structure was determined by spectroscopic analyses, and the absolute configuration of the chiral centers was determined by single-crystal X-ray diffraction analysis following crystallization. Hedopeptolide (1) inhibited the lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.