To investigate the potential for mollusks to serve as proxies for benthic respiration and hypoxia in the Gulf of Mexico (GOM), five gastropod (Conus austini Rehder and Abbott, 1951 and Strombus alatus Gmelin, 1791) and five bivalve (Pteria colymbus Röding, 1798 and Spondylus calcifer Carpenter, 1857) shells, from six Texas-Louisiana shelf localities during three periods from 1964 to 2009, were analyzed for oxygen and carbon stable isotopes (?18O and ?13C). These results were compared with isotopic measurements of nearby shelf waters, which reveal significant correlations between ?13C of dissolved inorganic carbon and dissolved oxygen. Low and correlative ?18O and ?13C values for coastal S. alatus indicate that the 7-m collection depth was mixed with low salinity surface waters. Low ?18O values in C. austini from 24 m trace a low salinity event related to hurricane camille in 1969. The carbon isotopic compositions of louisiana shelf C. austini do not exhibit the seasonal declines observed in the modern louisiana hypoxic zone, suggesting limited or no hypoxia off Terrebonne Bay from 1968 to 1971. Of note, the ?13C values of these Conus specimens and others reported in the literature are up to 1.5 higher than those of modern GOM Conus, indicating a rate of ?13CDIC reduction nearly twice that associated with intrusion of 13C-depleted anthropogenic co2 during the last four decades. We hypothesize that the larger rate of ?13CDIC depletion in Texas-Louisiana shelf waters reflects increasing oxidation of organic carbon fertilized by the increased flux of river-derived nutrients to the shelf.