Isotopes of epeiric sea carbonates are used to construct seawater records for modeling global changes in Paleozoic ocean chemistry, climate, and for intercontinental correlation. We present for the first time geochemical results of Paleozoic brachiopods (biogenic low-Mg calcite, bLMC) from open-ocean Permian–Carboniferous seamounts of Japan situated in the tropical mid-Panthalassic Ocean. Strontium isotope values of bLMC from the Panthalassic and Paleotethys Oceans are coupled with those of coeval specimens from epeiric seas of North America, Europe, and Russia (p = 0.393), but not with those of epeiric sea whole rocks (matrix aragonite/calcite, mAC; p = 0.029) and conodonts (biogenic apatite, bA; p = 0.031). Oxygen isotope values of bLMC from the Panthalassic and Paleotethys exhibit mixed results with studies of counterparts from epeiric seas (p = 0.596) reflecting overprinting of local environmental conditions on global trends. Carbon isotope values of bLMC and mAC from the Panthalassic and Paleotethys Oceans are generally dissimilar to those of coeval material from epeiric seas of North America, Europe, and Russia (p = 0.001 and 0.002, respectively). Factors such as water mass stratification, evaporation, dilution, depth, temperature, carbon burial and/or oxidation variations, and syndepositional diagenesis within the local environment probably influenced the chemistry of the fauna and accumulating sediments. This decoupling of carbon and oxygen isotope values from the open ocean with those from epeiric seas makes questionable the use of isotope results from epeiric seas for international correlation, constructing global seawater records, determining fluxes in the global carbon cycle, and for modeling climate changes and subsequently atmospheric carbon dioxide levels.