The authors examine the observed relationships between large-scale climate variability and concentrations of atmospheric carbon dioxide (CO2) in the Southern Hemisphere. The results reveal that month-to-month variations in the rate of change of atmospheric CO2 at Palmer Station on the Antarctic Peninsula are significantly related to fluctuations in the dominant mode of Southern Hemisphere atmospheric variability, the so-called Southern Annular Mode (SAM). A similar but weaker relationship between the SAM and atmospheric CO2 is evident at Syowa Station in eastern Antarctica, but not at the South Pole or stations located in Southern Hemisphere middle latitudes. Hence the SAM is most clearly related to fluctuations in atmospheric CO2 at locations that sample the westerly flow over the high latitudes of the Southern Ocean. Results based on CO2 flux estimates from the Atmospheric Tracer Transport Model Intercomparison Project (TransCom) suggest the observed relationships at least partially reflect the impact of the SAM on the flux of CO2 over the Southern Ocean.