In this paper, the stress in positive particles of a Li-ion battery during charging is obtained. The effects of the charging rates, charging modes, and structural parameters of the positive electrode on the stress are investigated. A mesoscopic electrochemical-mechanical coupling model for Li-ion battery is built and verified. The SOC, strain, and stress distributions in positive particles during the constant current (CC)-constant voltage (CV) charging process are calculated by the model. The results show that the stress in positive particles quickly increases at the CC charging stage, especially when the state of charge (SOC) of the battery exceeds 80%. Then it slowly increases at the CV charging stage. Under the CC-CV charging mode, the charging rate has little effect on the stress in positive particles at the end of charging. But the distance between particles, the particle radius, and the electrode thickness can affect the stress at the end of charging. The conclusions obtained could provide references for the design and optimization of the charging strategy and mesoscopic microstructure of LIBs.