AbstractThe Paleocene‐Eocene Thermal Maximum (PETM), a transient greenhouse climate interval spurred by a large release of carbon to the ocean‐atmosphere approximately 56 million years ago, provides a geological point of comparison for potential effects of anthropogenic carbon emission. Geochemical proxies and fossil assemblages offer insight into the continental shelf response to the PETM, but global ocean‐atmosphere models cannot resolve shelf processes at sufficient resolution for model‐data comparisons. We present high‐resolution simulations of the pre‐PETM and PETM North Atlantic basin using the Regional Ocean Modeling System (ROMS), including a resolved continental shelf along the eastern margin of North America in the Salisbury Embayment. ROMS' high‐resolution, terrain‐following coordinate system permits greater vertical resolution and eddy resolution along continental margins while also capturing open‐ocean processes. We find that during the PETM, benthic oxygen concentration ([O2]) in the Salisbury Embayment decreases 18% to an average state of year‐round mild hypoxia, while average benthic calcite saturation (Ω) declines from 4.4 to 2.3. These benthic decreases are driven largely by enhanced benthic oxic respiration, which occurs despite no increase in shelf productivity. Instead, increased respiration stems from less vigorous off‐shelf transport of organic matter due to (a) weakened along‐shelf water currents and (b) weakened coastal upwelling that forces productivity closer to the shelf seafloor. Model results do not include riverine inputs, which would have further lowered benthic [O2] and Ω. Our data suggest lowered benthic calcite saturation and mild hypoxia as an upper bound on the oxygenation state of the Salisbury Embayment seafloor during the PETM.