During the Paleocene-Eocene thermal maximum (PETM ∼55 Myr ago), prominent climatic and biogeochemical changes took place in the atmosphere, ocean, and on land. For example, deep-sea temperatures rose by 5°C to 6°C, while sea surface temperatures at high latitudes increased by up to 9°C. In the sedimentary record, the onset of the PETM is marked by widespread dissolution of calcium carbonate on the seafloor. In addition, there is evidence for globally higher humidity, precipitation and increased weathering during the PETM. Both calcium carbonate dissolution and enhanced weathering probably affected the seawater calcium concentration. Here we investigate implications that possible changes in the ocean's calcium inventory may have had on boron/calcium (B/Ca) and magnesium/calcium (Mg/Ca) ratios, which are used as proxies for deep water carbonate chemistry and temperature, respectively. We also examine effects on δ44Ca of seawater, which is used as an indicator for variations in the marine calcium cycle. We focus on the magnitude of change in the ocean's calcium ion concentration as a result of the carbon perturbation, which resulted in increased weathering fluxes and the dissolution of calcite on the ocean floor during the PETM. Different ranges of carbon input scenarios and their effect on ocean chemistry were examined using the Long-term Ocean-atmosphere-Sediment CArbon cycle Reservoir (LOSCAR) model. We found that under the most plausible scenario, the calcium ion concentration change (Δ[Ca2+]) was less than 0.7% and around 2% in the most extreme scenario. Our results show that B/Ca and Mg/Ca proxies were not affected within analytical precision by changes in oceanic calcium due to weathering and carbonate dissolution during the PETM. The most extreme scenario (Δ[Ca2+] = 2%) would result in ∼4 μmol kg−1 uncertainty in reconstruction of Δ[CO32−]. The same scenario affects the temperature reconstruction by ∼0.2°C. The effect on the ocean's calcium isotope budget was insignificant as well, resulting in Δδ44Casw of less than 0.05‰.