Midtropospheric CO_2 data from the Atmospheric Infrared Sounder (AIRS) are used in this study to explore the variability of CO_2 over the South Atlantic Ocean. It was found that the area-averaged CO_2 over the South Atlantic Ocean is less than that over South America by about 1 ppm during December–March. This CO_2 contrast is due to the large-scale vertical circulation over this region. During December–March, there is sinking motion over the South Atlantic Ocean. The sinking motion brings high-altitude air with a slightly lower concentration of CO_2 to the midtroposphere. Meanwhile, air rising over South America brings near-surface air with a higher concentration of CO_2 to the midtroposphere. As a result, the AIRS midtropospheric CO_2 concentration is lower over the South Atlantic Ocean than over South America during December–March. The detrended AIRS midtropospheric CO_2 difference correlates well with the inverted and detrended 400-hPa vertical pressure velocity difference between the South Atlantic and South America. Results obtained from this study demonstrate the strong impact of large-scale circulation on the vertical distribution of CO_2 in the free troposphere and suggest that midtropospheric CO_2 measurements can be used as an innovative observational constraint on the simulation of large-scale circulations in climate models