Context. CO isotopologue transitions are routinely observed in molecular clouds for the purpose of probing the column density of the gas and the elemental ratios of carbon and oxygen, in addition to tracing the kinematics of the environment.Aims. Our study is aimed at estimating the abundances, excitation temperatures, velocity field, and velocity dispersions of the three main CO isotopologues towards a subset of the Orion B molecular cloud, which includes IC 434, NGC 2023, and the Horsehead pillar.Methods. We used the Cramer Rao bound (CRB) technique to analyze and estimate the precision of the physical parameters in the framework of local-thermodynamic-equilibrium (LTE) excitation and radiative transfer with added white Gaussian noise. We propose a maximum likelihood estimator to infer the physical conditions from the 1–0 and 2–1 transitions of CO isotopologues. Simulations show that this estimator is unbiased and proves efficient for a common range of excitation temperatures and column densities (Tex > 6 K, N > 1014−1015  cm−2).Results. Contrary to general assumptions, the various CO isotopologues have distinct excitation temperatures and the line intensity ratios between different isotopologues do not accurately reflect the column density ratios. We find mean fractional abundances that are consistent with previous determinations towards other molecular clouds. However, significant local deviations are inferred, not only in regions exposed to the UV radiation field, but also in shielded regions. These deviations result from the competition between selective photodissociation, chemical fractionation, and depletion on grain surfaces. We observe that the velocity dispersion of the C18O emission is 10% smaller than that of 13CO. The substantial gain resulting from the simultaneous analysis of two different rotational transitions of the same species is rigorously quantified.Conclusions. The CRB technique is a promising avenue for analyzing the estimation of physical parameters from the fit of spectral lines. Future works will generalize its application to non-LTE excitation and radiative transfer methods.Read less <