Provided is a carbon monoxide (CO) dehydrogenase with increased oxygen resistance and/or enzyme activity, specifically, a mutant CO dehydrogenase with increased oxygen resistance and/or enzyme activity by mutating amino acid residues. The CO dehydrogenase may detoxify toxic carbon monoxide at room temperature and pressure by easily oxidizing carbon monoxide and converting the same into carbon dioxide, and may effectively oxidize carbon monoxide even in gas including oxygen. Furthermore, since it is possible to remove carbon monoxide, which is emitted in large quantities in industries such as petrochemical and steel industries, cigarette burning, household cooking, various boilers, and combustion, through cigarette filters, air purifiers, intake filters in household cooking equipment, gas boilers, etc. the CO dehydrogenase may be utilized in various ways.