We investigated the impact of persistent hypoxia on sediment chemistry by comparing total, reactive (extractible with 1 M hydroxylamine–hydrochloride in 25 % acetic acid), and dissolved forms of the redox-sensitive elements Mn, Fe, and As in cores recovered between 1982 and 2007 at two sites in the Lower St. Lawrence Estuary (LSLE) where the bottom water has been severely hypoxic since the early 1980s. The data reveal that the concentrations and the vertical distributions of total solid-phase and dissolved Mn as well as total solid-phase Fe and As were not significantly affected by persistent hypoxia. In contrast, the composition of solid-phase Fe and As changed significantly as did the pore-water concentrations of both these elements. The relative amounts of solid-phase reactive Fe and As increased, and the abundance of pyrite and pyritic–As decreased in the sediment layer that accumulated since 1982. We propose that persistent hypoxic conditions restrict the supply of oxygen to the sediment and increase the relative contribution of alternate electron acceptors—Mn(IV), Fe(III), and sulfate—to microbial oxidation of organic matter. In marine iron-rich environments, such as the LSLE sediment, increased sulfate reduction may promote conversion of less reactive Fe phases to more reactive Fe phases which, in turn, interfere with pyrite formation. Consequently, a chalcophile element such as As, which would normally be sequestered with authigenic pyrite, remains available for recycling across the oxic–anoxic boundary in the sediment.