Several small molecules and ions, notably carbon monoxide, cyanide, cyanate, and hydrogen sulfide, are potent inhibitors of Ni-containing carbon monoxide dehydrogenases (Ni-CODH) that catalyze very rapid, efficient redox interconversions of CO2 and CO. Protein film electrochemistry, which probes the dependence of steady-state catalytic rate over a wide potential range, reveals how these inhibitors target particular oxidation levels of Ni-CODH relating to intermediates (C-ox, C-red1, and C-red2) that have been established for the active site. The following properties are thus established: (1) CO suppresses CO2 reduction (CO is a product inhibitor), but its binding affinity decreases as the potential becomes more negative. (2) Cyanide totally inhibits CO oxidation, but its effect on CO2 reduction is limited to a narrow potential region (between -0.5 and -0.6 V), below which CO2 reduction activity is restored. (3) Cyanate is a strong inhibitor of CO2 reduction but inhibits CO oxidation only within a narrow potential range just above the CO2/CO thermodynamic potential-EPR spectra confirm that cyanate binds selectively to C-red2. (4) Hydrogen sulfide (H2S/HS-) inhibits CO oxidation but not CO2 reduction-the complex on/off characteristics are consistent with it binding at the same oxidation level as C-ox and forming a modified version of this inactive state rather than reacting directly with C-red1. The results provide a new perspective on the properties of different catalytic intermediates of Ni-CODH-uniting and clarifying many previous investigations.