Atmospheric Infrared Sounder (AIRS) offers a unique opportunity to investigate the variability of mid-tropospheric CO2 over the entire globe. In this paper, we use AIRS data to examine the interannual variability of CO2 and find significant correlations between AIRS mid-tropospheric CO2 and large-scale atmospheric dynamics. During El Niño events, mid-tropospheric CO2 over the central Pacific Ocean is enhanced whereas it is reduced over the western Pacific Ocean as a result of the change in the Walker circulation. The variation of AIRS CO2 in the high latitudes of the northern hemisphere is closely related to the strength of the northern hemispheric annular mode. These results contribute to a better understanding of the influence of large-scale dynamics on tracer distributions.