The adsorption, dissociation, and diffusion of CO on the α-U(001) surface were studied using density functional theory with the generalized gradient approximation (GGA). The calculation results show that a CU3OU2-type molecular chemisorption of CO is favored with adsorption energies of 1.78-1.99 eV. The U atoms of the surface layer are found to move upwards after adsorption coupled with a rumpling of the surface layer. The interaction between the U atoms and a CO molecule results mainly from the population of the CO 2π* LUMO by U electrons and the CO 2π*/5σ/1π-U 6d orbital hybridization. Dissociative adsorption is energetically more favored than molecular adsorption with adsorption energies of 2.71 and 3.08 eVfor the h1(C)+h2(O) and h1(C)+h1(O) (h: hollowsite) dissociative configurations, respectively. The diffusion barriers of C and O atoms between two adjacent threefold hollow sites are found to be 0.57 and 0.14 eV, respectively, which indicates that the on-surface diffusion ofO atoms is more easily achieved than that of C atoms.