We provide quantitative estimates for the spatial variability of CO2, crucial for assessing representativeness of observations. Spatial variability determines the mismatch between point observations and spatial averages simulated by models or observed from space-borne sensors. Such “representation errors” must be properly specified in determining the leverage of observations to retrieve surface fluxes or to validate space-borne sensors. We empirically derive the spatial variability and representation errors for tropospheric CO2 over the North American continent and the Pacific Ocean, using in-situ observations from extensive aircraft missions. The spatial variability and representation error of CO2 is smaller over the Pacific than the continent, particularly in the lowest altitudes, and decreases with altitude. Representation errors resulting from spatial variability in the summer continental PBL are as large as 1∼2 ppmv for typical grid resolutions used in current models for inverse analyses.