The use of optical circular multipass absorption cells (CMPAC) in an open-path configuration enables the sampling free analysis of cylindrical gas flows with high temporal resolution and only minimal disturbances to the sample gas in the pipe. Combined with their robust unibody design, CMPACs are a good option for many applications in atmospheric research and industrial process monitoring. When deployed in an open-path configuration, the effects of inhomogeneities in the gas temperature and composition have to be evaluated to ensure that the resulting measurement error is acceptable for a given application. Such an evaluation needs to consider the deviations caused by spectroscopic effects, e.g., nonlinear effects of temperature variations on the intensity of the spectral line, as well as the interaction of the temperature and concentration field with the characteristic laser beam pattern of the CMPAC. In this work we demonstrate this novel combined evaluation approach for the CMPAC used as part of the tunable diode laser absorption spectroscopy (TDLAS) reference hygrometer in PTB’sdynH2Osetup for the characterization of the dynamic response behavior of hygrometers. For this, we measured spatially resolved, 2D temperature and H2O concentration distributions, and combined them with spatially resolved simulated spectra to evaluate the inhomogeneity effects on the line area of the used H2O spectral line at 7299.43 cm−1. Our results indicate that fordynH2O, the deviations caused by the interaction between large concentration heterogeneities and the characteristic sampling of the beam pattern of the CMPAC are three orders of magnitude larger than deviations caused by small temperature heterogeneity induced spectroscopic effects. We also deduce that the assumption that the “path-integrated” H2O concentration derived with the open-path CMPAC setup represents an accurate H2O area average in the flow section covered by the CMPAC in fact shows significant differences of up to 16% and hence does not hold true when large H2O concentration gradients are present.