Abstract Seepage of methane and oil is widespread at active and passive continental margins worldwide. Large-scale methane release may have caused bottom water oxygen depletion and acidification in the geological past, but direct evidence of low-oxygen conditions caused by methane leakage in natural systems is scarce. Here we report on the geochemical composition of sediments of two deepwater seep sites (>1700 m) from the South China Sea. The δ34S values of chromium reducible sulfur (δ34SCRS), δ13C values of total inorganic carbon (δ13CTIC), total sulfur (TS) and total organic carbon (TOC) contents, as well as redox-sensitive elements (Fe, U, and Mn) are used to constrain the intensity of fluid seepage and its impact on bottom water redox conditions. Sediment horizons affected by methane seepage are characterized by relatively high TS/TOC ratios (>1.4), low δ13CTIC values ( 22‰). The identified horizons show elevated authigenic U contents, high U/Th, as well as low Mn/Al ratios, suggesting oxygen depletion during their deposition. It is shown that local oxygen concentration of bottom waters was related to methane flux, with periods of larger methane release initiating during the Last Glacial Maximum. Much oxygen was apparently consumed during times of intense methane seepage, resulting in low oxygen conditions of bottom waters – conditions that persisted for ten thousand years and more. Our observations suggest that the interplay of flow intensity and microbial processes at seeps can locally affect the oxygen concentration in the deep ocean. The impact of microbial methane consumption on the oxygen concentration in the deep ocean should consequently be considered when looking into potential effects of future warming of the ocean, as more gas hydrate is susceptible to destabilization during ocean warming.