Fluctuations in atmospheric p CO 2 may have played the key role in global climate throughout Earth’s history. For the quantification of past variations in atmospheric p CO 2 , several geological proxy approaches and geochemical models have been developed. Here, we evaluate a new CO2 proxy approach that is based on the triple oxygen isotope composition (16O, 17O, 18O) of skeletal apatite of terrestrial mammals. Our approach utilizes the relation between an anomaly in 17O of tropospheric air O2 and atmospheric p CO 2 . The anomaly is transferred from inhaled air O2 to skeletal apatite of mammals. Hence, triple oxygen isotope data of mammalian bioapatite provide information regarding p CO 2 during the animal’s lifetime. The approach was calibrated with a detailed mass balance model that was verified by analyses on a set of recent mammals. We evaluate the potential of this new independent terrestrial paleo-CO2 proxy in a case study including Eocene to Miocene samples. The present investigation provides promising results that are in good agreement with existing proxy- and model data. The uncertainty intrinsic to the proxy is mainly due to uncertainties in physiological parameters.