The new single-pixel TROPESS (TRopospheric Ozone and its Precursors from Earth System Sounding) profile retrievals of carbon monoxide (CO) from the Cross-track Infrared Sounder (CrIS) are evaluated using vertical profiles of in situ observations from the National Oceanic and Atmospheric Administration (NOAA) Global Monitoring Laboratory (GML) aircraft program and from the Atmospheric Tomography Mission (ATom) campaigns. The TROPESS optimal estimation retrievals are produced using the MUSES (MUlti-SpEctra, MUlti-SpEcies, MUlti-Sensors) algorithm, which has heritage from retrieval algorithms developed for the EOS/Aura Tropospheric Emission Spectrometer (TES). TROPESS products provide retrieval diagnostics and error covariance matrices that propagate instrument noise as well as the uncertainties from sequential retrievals of parameters such as temperature and water vapor that are required to estimate the carbon monoxide profiles. The validation approach used here evaluates biases in column and profile values as well as the validity of the retrieval error estimates using the mean and variance of the compared satellite and aircraft observations. CrIS–NOAA GML comparisons had biases of 0.6 % for partial column average volume mixing ratios (VMRs) and (2.3, 0.9, −4.5) % for VMRs at (750, 511, 287) hPa vertical levels, respectively, with standard deviations from 9 % to 14 %. CrIS–ATom comparisons had biases of −0.04 % for partial column and (2.2, 0.5, −3.0) % for (750, 511, 287) hPa vertical levels, respectively, with standard deviations from 6 % to 10 %. The reported observational errors for TROPESS/CrIS CO profiles have the expected behavior with respect to the vertical pattern in standard deviation of the comparisons. These comparison results give us confidence in the use of TROPESS/CrIS CO profiles and error characterization for continuing the multi-decadal record of satellite CO observations.