Comparisons are made between mid-tropospheric Tropospheric Emission Spectrometer (TES) carbon dioxide (CO<sub>2</sub>) satellite measurements and ocean profiles from three Hiaper Pole-to-Pole Observations (HIPPO) campaigns and land aircraft profiles from the United States Southern Great Plains (SGP) Atmospheric Radiation Measurement (ARM) site over a 4-yr period. These comparisons are used to characterize the bias in the TES CO<sub>2</sub> estimates and to assess whether calculated and actual uncertainties and sensitivities are consistent. The HIPPO dataset is one of the few datasets spanning the altitude range where TES CO<sub>2</sub> estimates are sensitive, which is especially important for characterization of biases. We find that TES CO<sub>2</sub> estimates capture the seasonal and latitudinal gradients observed by HIPPO CO<sub>2</sub> measurements; actual errors range from 0.8–1.2 ppm, depending on the campaign, and are approximately 1.4 times larger than the predicted errors. The bias of TES versus HIPPO is within 0.85 ppm for each of the 3 campaigns; however several of the sub-tropical TES CO<sub>2</sub> estimates are lower than expected based on the calculated errors. Comparisons of aircraft flask profiles, which are measured from the surface to 5 km, to TES CO<sub>2</sub> at the SGP ARM site show good agreement with an overall bias of 0.1 ppm and rms of 1.0 ppm. We also find that the predicted sensitivity of the TES CO<sub>2</sub> estimates is too high, which results from using a multi-step retrieval for CO<sub>2</sub> and temperature. We find that the averaging kernel in the TES product corrected by a pressure-dependent factor accurately reflects the sensitivity of the TES CO<sub>2</sub> product.