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Chemical short-range order (CSRO) is a typical microstructural characteristic commonly found in multi-principal element alloys (MPEAs). For MPEAs with the face-centered cubic (FCC) structure, the presence of CSRO has been verified and characterized meticulously by using electron microscope. However, it is still challenging to reveal the effect of CSRO structure on the deformation microstructure and micromechanical behavior of those alloys. By applying atomic scale simulations, this study explores the micromechanical behavior of an equiatomic CoCrNi medium entropy alloy with random solid solution and three different degrees of CSRO under plane strain compression, respectively. The results show that CSRO can effectively promote planar slip of dislocations in the FCC matrix and elevate flow stress of the alloy. The planar slip and stacking of partial dislocations then lead to the formation of hexagonal-close-packed (HCP) structure lamellae. CSRO also modulates the morphology of dislocations. When dislocations cut through CSRO, it hinders the movement of dislocations while being destroyed by atomic plastic flow, causing CSRO and atomic clusters at the interface of the matrix to embed each other and generate antiphase boundaries which can significantly enhance the bulk yield strength. These findings provide fundamental insights into the interaction between CSRO and dislocations in CoCrNi MEA, guiding the design of MPEAs with superior combinations of strength and ductility. [Display omitted] • Interaction between chemical short-range order (CSRO) and dislocations in the CoCrNi MEA is unraveled. • Deformation mechanisms depend on the degree of CSRO. • Plastic deformation deteriorates CSRO. The more significant the CSRO, the easier it is to be destroyed with deformation. [ABSTRACT FROM AUTHOR]