AbstractUnderstanding the cellular and molecular responses of stony corals to ocean acidification is key to predicting their ability to calcify under projected high CO2 conditions. Of specific interest are the links between biomineralization proteins and the precipitation of new calcium carbonate (CaCO3), which potentially can provide a better understanding of the biomineralization process. We have assessed the effects of increased CO2 on the calcification process in cell cultures of the stony coral, Stylophora pistillata, reared in nutrient‐enriched artificial seawater at four pCO2 levels and two glucose concentrations. Dispersed S. pistillata cells grown at low (400 ppmV) and moderate (700 ppmV) pCO2 re‐aggregate into proto‐polyps and precipitate CaCO3. When grown at pCO2 levels of 1000 ppmV and 2000 ppmV, the cells up‐regulate genes for two highly acidic proteins as well as a carbonic anhydrase, but down‐regulate long term cadherin protein production and minimize proto‐polyp formation, and exhibit a significant decrease in measurable CaCO3 precipitation. However, cell cultures precipitate CaCO3 in all treatments, even at slightly undersaturated conditions (Ωaragonite < 0.95). Glucose addition does not influence either biomineralization gene expression or calcification rate. Measured δ11B of the mineral phase, as a proxy of the pH at the calcifying sites, is out of equilibrium with the ambient seawater medium surrounding the cells and proto‐polyps, suggesting pH is elevated in the micro‐environment of the precipitating mineral. Our results suggest that coral cells possess molecular mechanisms to help compensate for the effects of ocean acidification within the bounds projected in the coming century.