Three new unique sesquiterpenes, euryspongins A-C (1-3), were isolated from a marine sponge Euryspongia sp. collected at Iriomote Island, Okinawa, Japan. Compound 1 possessed a bicyclic furanosesquiterpene structure with six- and eight-membered rings, whereas compounds 2 and 3 had an α,β-unsaturated-γ-lactone ring instead of the furan ring in 1. Only five natural products in this class have been reported, and compounds 1-3 are the sixth-eighth examples of natural products. Compounds 1-3 had no inhibition effect against PTP1B, an important target enzyme for the treatment of diabetes, while the dehydro derivative of 1 [dehydroeuryspongin A (4)] exhibited inhibitory activity (IC(50)=3.6 μM).