A large body of paleoceanographic data for the Paleocene-Eocene Thermal Maximum (PETM) is based on foraminiferal stable carbon and oxygen isotope composition (δ13C and δ18O). However, the proxy records could be biased due to a “pH effect” on stable isotopes during times when the ocean became more acidic, as has been demonstrated for modern planktonic foraminifera. In this paper, we calculate the possible ranges of the pH effect on δ13C and δ18O during the PETM based on the relative pH decline (ΔpH) from the preperturbation steady state simulated by a carbon cycle model and the empirical relationships obtained from culture experiments with planktonic foraminifera. The model is configured with Eocene paleogeography and simulates ΔpH for surface, intermediate, and deep water in the major ocean basins in response to various carbon input scenarios (2000 to 5000 Pg C). For an array of scenarios, the modeled ΔpH of the surface ocean ranges from 0.1 to 0.28 units. This suggests that δ13C of planktonic foraminifera may be increased by up to 2.1‰ and δ18O may be increased by up to 0.7‰ (corresponding to over 3°C error in paleotemperature estimate). Under conditions in which the model best simulates the global CaCO3 dissolution pattern, we find marked differences in the deep-sea ΔpH between the Atlantic (−0.4) and Pacific oceans (−0.1). This would imply that the magnitude of the negative δ13C and δ18O excursions of benthic foraminifera in the Atlantic Ocean was dampened by up to 2.8‰ and 0.9‰ at maximum, respectively, relative to a constant pH scenario.