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From the mechanical perspectives, the influence of point defects is generally considered at high temperature, especially when the creep deformation dominates. Here, we show the stress-induced reversible oxygen vacancy migration in CuO nanowires at room temperature, causing the unanticipated anelastic deformation. The anelastic strain is associated with the nucleation of oxygen-deficient CuO x phase, which gradually transforms back to CuO after stress releasing, leading to the gradual recovery of the nanowire shape. Detailed analysis reveals an oxygen deficient metastable CuO x phase that has been overlooked in the literatures. Both theoretical and experimental investigations faithfully predict the oxygen vacancy diffusion pathways in CuO. Our finding facilitates a better understanding of the complicated mechanical behaviors in materials, which could also be relevant across multiple scientific disciplines, such as high-temperature superconductivity and solid-state chemistry in Cu-O compounds, etc. The effect of point defects on mechanical behaviour of materials is generally considered at high temperatures. This work reports a reversible stress-induced migration of point defects during anelastic deformation in CuO nanowires at room temperature resulting from heterogeneous strain distribution.