The Abrahamskraal Formation of South Africa has a diverse middle Permian (Guadalupian) fossil tetrapod fauna comprising largely basal therapsids and pareiasaurian parareptiles. Knowledge on the paleoecology of these animals is limited because inferences of many ecological traits in mid-Permian tetrapods are based on deductions from morphology. While it is widely accepted that the rhinesuchid amphibians were aquatic, the ecological lifestyle of pareiasaurs and dinocephalian therapsids remains uncertain. To investigate the ecological roles of different middle Permian tetrapod taxa we studied stable oxygen isotope compositions of phosphate from teeth and bones as a proxy for water dependence. Our results reveal similar delta O-18(p) values for pareiasaurs, the dinocephalian Anteosaurus, and therocephalians, with a range of values similar to those of extant terrestrial species. The consistent delta O-18(p) values for pareiasaurs strengthen our interpretation of a terrestrial lifestyle for these parareptiles, but the lower Anteosaurus delta O-18(p) values might question the interpretation and a larger sample size may result in a more conclusive outcome. These results conclude the debate on the ecology of middle Permian pareiasaurs. A terrestrial lifestyle is applicable only to the middle Permian species and a different lifestyle is possible for pareiasaurs species that lived after the end Capitanian extinction.