Abstract: First-principles calculations were performed to investigate the mechanical properties of ZnO nanowires and to study the doping and size effects. A series of strains were applied to ZnO nanowires in the axial direction and the elastic moduli of ZnO nanowires were obtained from the energy versus strain curves. Pure and Mn-doped ZnO nanowires with three different diameters (1.14, 1.43, and 1.74 nm) were studied. It is found that the elastic moduli of the ZnO nanowires are 146.5, 146.6, and 143.9 GPa, respectively, which are slightly larger than that of the bulk (140.1 GPa), and they increase as the diameter decreases. The elastic moduli of the Mn-doped ZnO nanowires are 137.6, 141.8, and 141.0 GPa, which are slightly lower than those of the undoped ones by 6.1%, 3.3%, and 2.0%, respectively. The mechanisms of doping and size effect were discussed in terms of chemical bonding and geometry considerations.