Hypoxia and associated acidification are growing concerns for ecosystems and biogeochemical cycles in the coastal zone. The northern Gulf of Mexico (nGoM) has experienced large seasonal hypoxia for decades linked to the eutrophication of the continental shelf fueled by the Mississippi River nutrient discharge. Sediments play a key role in maintaining hypoxic and acidified bottom waters, but this role is still not completely understood. In the summer 2017, when the surface area of the hypoxic zone in the nGoM was the largest ever recorded, we investigated four stations on the continental shelf differentially influenced by river inputs of the Mississippi-Atchafalaya River System and seasonal hypoxia. We investigated diagenetic processes under normoxic, hypoxic, and nearly anoxic bottom waters by coupling amperometric, potentiometric, and voltammetric microprofiling with high-resolution diffusive equilibrium in thin-films (DET) profiles and porewater analyses. In addition, we used a time-series of bottom-water dissolved oxygen from May to November 2017, which indicated intense O2 consumption in bottom waters related to organic carbon recycling. At the sediment-water interface (SWI), we found that oxygen consumption linked to organic matter recycling was large with diffusive oxygen uptake (DOU) of 8 and 14 mmol m–2 d–1, except when the oxygen concentration was near anoxia (5 mmol m–2 d–1). Except at the station located near the Mississippi river outlet, the downcore pore water sulfate concentration decrease was limited, with little increase in alkalinity, dissolved inorganic carbon (DIC), ammonium, and phosphate suggesting that low oxygen conditions did not promote anoxic diagenesis as anticipated. We attributed the low anoxic diagenesis intensity to a limitation in organic substrate supply, possibly linked to the reduction of bioturbation during the hypoxic spring and summer.