Reconstructing the oxygen content at the ocean floor provides insight into ocean circulation, ventilation, and carbon storage in the deep sea. The microbial breakdown of organic carbon within marine sediment through aerobic respiration consumes oxygen in the pore fluid and releases dissolved inorganic carbon. The offset in the carbon isotopic composition, δ13C, of epifaunal and infaunal foraminifera, Δδ13C, is considered to reflect the aerobic respiration of organic carbon and can be used to reconstruct the oxygen content of the bottom water. Previous work provided an empirical calibration that was suggested to be valid for oxygen reconstructions between 55 and 235 μmol kg−1. In this study, we apply a biogeochemical reactive transport model (RTM) to extend and update this calibration, allowing for the reconstruction of oxygen concentrations ([O2]) up to ∼300 μmol kg−1. Using the RTM and new bottom water [O2] and pore fluid measurements from Iberian Margin sediment cores, we also demonstrate that the calibration between the Δδ13C and bottom water [O2] must account for the coupled changes in the carbon system due to the respiration of organic carbon in the overlying ocean including the concentration and carbon isotopic composition of the dissolved inorganic carbon, and the δ13C of the organic carbon within the sediment column. We apply the improved calibration to reconstruct the changes in oxygen content at International Ocean Discovery Program (IODP) Site U1385 in the deep North Atlantic over the past 1.5 Myr.