The polyethylene terephthalate (PET) foam sandwich structure is widely used for ships and for studying the influence of the seawater environment on its mechanical properties as an important way to evaluate its safety performance. To study the effect of the seawater environment on the mechanical properties of the PET foam sandwich structure, this paper mainly studies the static properties, interlayer cracking properties, and fatigue failure properties of the PET foam sandwich structure under the simulated seawater environment at a constant temperature of 40°C. The compressive properties test, tensile properties test, three-point bending properties test, double cantilever beam test, and four-point test were carried out on PET foam specimens, glass fiber reinforced plastic (GFRP) panel specimens, and PET foam sandwich structure specimens with different immersion times. The multiphysics software COMSOL was used to model and analyze the mode I interlayer cracking properties of the PET foam sandwich structure. The comparative analysis of the experimental results shows that the seawater environment has an effect on the compression properties of PET foam, the tensile and flexural properties of GFRP panels, and the interlayer cracking properties of the PET foam sandwich structure, and as the immersion time is extended, the effect is more obvious. Seawater immersion can also lead to a reduction in the fatigue life and ultimate fatigue of the PET foam sandwich structure.