The integrity of the cement sheath is susceptible to failure during multi-stage fracturing. In this study, the failure mechanisms of cement sheath integrity during multi-stage fracturing in the A offshore tight oil reservoir wells were investigated. The cement samples were subject to triaxial compression test (TCT), triaxial cyclic loading test (TCLT), and permeability test. A full-scale device was constructed for cement sheath integrity experiments. Additionally, a 3-D finite element model was developed to simulate the interface debonding and the subsequent growth of micro-annuli throughout multi-stage fracturing. The results revealed that TCLT induced cumulative plastic deformation in the cement samples, resulting in a 10.7% decrease in triaxial compressive strength, an 8.3% decrease in elastic modulus, and a 150% increase in permeability. Despite these significant variations, no serious damage was caused to the cement sheath matrix. It was observed that gas leakage occurred at the 8th, 10th, and 14th cycles under cyclic loading with upper limits of 70 MPa, 80 MPa, and 90 MPa, respectively. After 15 cycles, the experimentally measured widths of micro-annuli were 117 μm, 178 μm, and 212 μm, which were in good agreement with simulation results of 130 μm, 165 μm, and 205 μm, respectively. These findings elucidate the causes of cement sheath integrity failure, providing insights into the failure mechanisms of cement sheath integrity during multi-stage fracturing.