Three unique sesquiterpenes, named euryspongins A-C (1-3), have been isolated from the marine sponge Euryspongia sp. The absolute configuration of 1 was assigned as (4R,6R,9S) by comparing its experimental Electronic Circular Dichroism (ECD) spectrum with the calculated ECD spectra of both enantiomers, and the absolute configurations of 2, 3 and artifact 4 were suggested on the basis of that of 1 by assuming common biogenesis of 1-3. These absolute configurations were opposite to those depicted in the previous communication. Further separation of the remaining fractions lead to the isolation of a new C11-polyketide, named as eurydiene (5), together with a known C11-polyketide, nakitriol (6). The structure of 5 was assigned on the basis of its spectroscopic data as a bicyclic alcohol with a diene side chain. Dehydroeuryspongin A (4) inhibited protein tyrosine phosphatase 1B (PTP1B), an important target enzyme for the treatment of type II diabetes and obesity, with an IC50 value of 3.58μM. Moreover, compound 4 did not inhibit the proliferation of human hepatoma Huh-7 cells at 100μM. One of the locations in which PTP1B has been detected is hepatocytes. Compounds 1-3, 5, and 6 were not active against PTP1B. The growth of human colon (HCT-15) and T-cell lymphoma (Jurkat) cells was not disturbed by compounds 1-6.