Density functional theory (DFT) calculations were carried out on five transition metals (Co, Ni, Pd, Rh, Ru) to test their activities toward the biomimetic carbon dioxide hydration reaction. Periodic plane-wave calculations demonstrated the formation of surface species in accordance with the mechanism of the reaction known for α-carbonic anhydrase action. To determine different activation barriers for the different elementary steps involved in the reaction, DFT calculations using a cluster model of transition metals with Gaussian-type orbitals were carried out. The periodic and cluster calculations were found to correspond to a mechanism of the reaction constitituting seven steps, namely, surface adsorption of H₂O, deprotonation and surface OH formation, adsorption of CO₂, OH attack on adsorbed CO₂, proton transfer, H₂O attack on surface HCO₃^– complex, and HCO₃^– displacement by H₂O. The behaviors of the metals were found to be different in a vacuum and in the solvated state, with Co being the best potential candidate for the biomimetic CO₂ hydration reaction in a vacuum and Ru being the best candidate for the reaction in solution.