While size effects in composite structures have been widely studied under quasi-static uniaxial loading, their influence under fatigue conditions, particularly in the presence of multiaxial stress states and elevated temperatures, remains insufficiently understood. This study investigates the fatigue behaviour of thick-walled ±45° braided glass fibre-reinforced polyurethane composite box structures under varying temperature and loading conditions. A combined experimental approach is adopted, coupling quasi-static and fatigue tests on large-scale structures with reference data from standardised coupon specimens. The influence of temperature (23–80 °C) and multiaxial shear–compression loading is systematically evaluated. The results demonstrate a significant temperature-dependent decrease in compressive strength and fatigue life, with a linear degradation trend that aligns closely between the box structure and coupon data. Under moderate multiaxial conditions, the fatigue life of box structures is not significantly impaired compared to uniaxial test coupon specimens. Complementary non-destructive testing using air-coupled ultrasound confirms these trends, demonstrating that guided-wave phase-velocity measurements capture the evolution of anisotropic damage and are therefore suitable for in situ structural health monitoring applications. Furthermore, these findings highlight that (i) the temperature-dependent fatigue behaviour of thick-walled composites can be predicted using small-scale coupon data and (ii) small shear components have a limited impact on fatigue life within the studied loading regime.