13C shieldings, δ(13C), 17O shieldings, δ(17O), and 18O isotope effects on 13C shieldings, 1Δ13C(18O/16O), of carbon monoxide (99.7% 13C, 0.9% 17O, and 11.8% 18O enriched) in a variety of solvents and of the Fe−C−O unit of several carbonmonoxy hemoprotein models with varying polar and steric effects of the distal organic superstructure and constraints of the proximal side are reported. This enables, first, comparisons with hemoproteins, C−O vibrational frequencies, ν(C−O), and X-ray structural data to be made; second, to investigate whether polarizable CO is an adequate model for distal ligand effects in carbonmonoxy heme proteins and synthetic model compounds; third, to investigate the effect of electronic perturbation within the heme pocket and pocket deformation on δ(13C), δ(17O), 1Δ13C(18O/16O), and ν(C−O). A variety of solvents with varying dielectric constants and solvation abilities appears to have negligible effect on δ(17O), δ(13C), and 1Δ13C(18O/16O) and little direct effect on ν(C−O) of dissolved carbon monoxide. On the contrary, 13C and 17O shieldings of several carbonmonoxy hemoprotein models vary widely and an excellent correlation was found between the infrared C−O vibrational frequencies and 13C shieldings and a reasonable correlation with 18O isotope effects on 13C shieldings. The 13C shieldings of heme models cover a 4.0 ppm range which is extended to 7.0 ppm when several HbCO and MbCO species at different pHs are included. The latter were found to obey a similar linear δ(13C) vs ν(C−O) relationship. ν(C−O), δ(13C), and 1Δ13C(18O/16O) parameters of heme model compounds reflect similar interaction which is primarily the modulation of π back-bonding from Fe dπ to CO π* orbital by the distal pocket polar interactions. Our results suggest that, contrary to earlier claims, polarizable carbon monoxide is not an adequate model for distal ligand effects in carbonmonoxy hemoproteins and synthetic model compounds. Very probably this is caused by the large effect of the electric field on the back-bonding and the large polarizability of the π subsystem of the Fe−C−O unit. The 17O shieldings of heme models cover a range of 17 ppm which is extended to 24 ppm when selected heme proteins are included. The lack of correlation between δ(13C) and δ(17O) suggests that the two probes do not reflect a similar type of electronic and structural perturbation. δ(17O) is not primarily influenced by the local distal field interactions and does not correlate with any single structural property of the Fe−C−O unit; however, atropisomerism and deformation of the porphyrin geometry appear to play a significant role.