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Amfilochia Bay (Eastern Amvrakikos Gulf, Western Greece), a complex marine area affected by tectonism, was investigated for seabed seepage manifestations and for possible inter-relationships between shallow gas accumulations and hypoxia. For this purpose, an integrated research methodology that combined geophysical, geochemical, and hydrographic surveys was applied. Marine geophysical and bathymetric surveys led to the discovery of a gas-induced pockmark group in the study area. Oceanographic surveying confirmed that the bay is hypoxic/anoxic below a depth of 15 m (dissolved oxygen from ~4 to 60 μM). Very weak CH4 seepage was detected in correspondence to the pockmark group that seemed to slightly enhance the hypoxic environment locally and close to the seabed, with no effect in shallower waters and the oxycline. Methane isotopic analysis showed variable carbon isotopic composition (from −41‰ to −86‰) which could be either related to differential CH4 oxidation or mixing between microbial and thermogenic gas. However, the pathway of degassing is clearly related to the fault-controlled pockmark group. A protrusion mound, which has erroneously been reported as a submarine “volcano” since 1876, could be the result of mud volcanism based on the geophysical data of this study.