This study investigated the effect of moisture absorption on the mechanical performance of polyurethane sandwich composites. The core material was a closed cell polyurethane foam. Face sheets were made of E-glass/polyurethane composite laminates. Vacuum-assisted resin transfer molding process was used to manufacture specimens for testing. The foam core, laminates, and sandwich composites were submerged in salt water for prolonged periods of time. Mechanical property degradation due to moisture absorption for each constituent was evaluated. Compression test was performed on the foam core samples. Laminates were evaluated by three-point bending tests. The interfacial bond strength in the sandwich structure was evaluated by double cantilever beam mode-I interfacial fracture test. The testing results revealed that the effect of salt water exposure on the compressive properties of the foam core is insignificant. The flexural modulus of polyurethane laminates degraded 8.9% and flexural strength degraded 13.0% after 166 days in 50% salinity salt water at 34°C conditioning. The interfacial fracture toughness of polyurethane sandwich composites degraded 22.4% after 166 days in 50% salinity salt water at 34°C conditioning.