Strongly deformed greenschist facies carbonate rocks in western Arizona exhibit large 18O and 13C depletions relative to unmetamorphosed correlative rocks in northeastern Arizona. Unmetamorphosed Permian Kaibab Formation carbonates on the Colorado Plateau yield δ13C values of +1‰ to +5‰ and δ18O values of +28‰ to +37‰. In contrast, greenschist facies Kaibab Formation in the Little Harquahala and Granite Wash Mountains yields δ13C values of −6‰ to +4‰ and δ18O values of +9‰ to +24‰. The magnitude of the observed 13C and 18O depletions cannot be explained by decarbonation reactions and requires extensive exchange with low δ13C and δ18O fluids. The 13C depletions may reflect isotopic exchange with lower δ13C carbonate in the underlying Paleozoic section and exchange with CO2 derived from oxidation of methane via reaction with hematite or sulfate in interbedded rocks. These data demonstrate that large 13C and 18O depletions can occur in strongly deformed terranes during very low-grade metamorphism. Depletions in 13C and 18O observed in some high-grade metamorphic terranes may be inherited from much lower metamorphic grades.