Objective To construct a three-dimensional (3D) solid model of the cortical bone including osteons, verify the stress concentration effect of osteons, simulate and predict the stress concentration location under fatigue using finite element analysis (FEA). Methods The 3D solid model of the cortical bone including osteons was constructed in Pro/E wildfire 5.0, and local stress and strain distributions in the cortical bone under different axial compression were calculated and analyzed in ANSYS 12.0. Fatigue simulation on the selected locations was conducted to evaluate fatigue status of the model subjected to different fatigue loading intensities. Results Obvious stress concentration at the junction of osteon and the interstitical bone appeared under axial compressive loads, and the percentage of pathological local strain in the cortical bone increased with the axial compression increasing. Fatigue simulation on the selected locations demonstrated that bone fatigue risk during physiological or daily activities was very low, while a high fatigue or fracture risk might occur during high-intensity exercises or training. Conclusions The 3D solid model of the cortical bone including osteons is successfully established, the stress concentration effect of osteons is verified, and the location of bone fatigue damage under strenuous exercise and its risk are predicted. These experimental results can provide references for training management and athletic fatigue damage prevention in military recruits and long distance running athletes.