Abstract: Ni-based single crystal superalloys are key materials used in the manufacturing of turbine blades for aerospace engines and heavy-duty gas turbines. The turbine blade suffers severe low cycle fatigue (LCF) loading during operation. Previous experimental studies have demonstrated that the addition of rhenium (Re) effectively enhances the fatigue mechanical properties of superalloys. However, the underlying reasons for this improvement have not been clearly explained. In this work, the effects of Re on the mechanical properties and microstructure evolution of Ni-based single crystal superalloys under LCF loading are investigated by molecular dynamics simulations, the main reasons why Re improves the LCF mechanical properties and fatigue life of Ni-based single crystal superalloys are explained from the atomic scale. The results show that the addition of Re to the Ni-based single crystal superalloys can effectively increase the cyclic stress amplitude and improve the plastic deformation resistance. Additionally, it can reduce the plastic strain and plastic strain energy density of the superalloys. In terms of microstructure, the addition of Re can reduce the dislocation density of the superalloys, resulting in less plastic deformation in the γ' precipitate phase, and thus reduce the plastic strain energy density of the superalloys. This is mainly due to the pinning and dragging effects of Re atoms on the dislocation motion, which lead to a stronger hindrance of the dislocation motion, resulting in higher cyclic stress amplitude and less plastic deformation of the superalloys with Re addition. In addition, due to the pinning and dragging effects of Re on the dislocation motion, the microstructure stability of the superalloys with Re addition is improved, resulting in stronger fatigue resistance and longer fatigue life. The research is helpful to further understand the LCF mechanical properties and Re effect at the atomic scale. Moreover, it can also provide theoretical support for the development and design of new generation Ni-based single crystal superalloys.