This study analyzes the mechanical behavior of low density polyethylene foam core sandwich panels subjected to edgewise compression. In order to monitor panel response to buckling, strains generated in the facesheets and overall out-of-plane deformations are measured with strain gages and projection moiré, respectively. A finite element (FE) model simulating the experimental test is developed. Numerical results are compared with moiré measurements. After having been validated against experimental evidence, the FE model is parameterized, and a trade study is carried out to investigate to what extent the structural response of the panel depends on the sandwich wall construction and facesheet/core interface defects. The projection moiré set-up utilized in this research is able to capture the sudden and very localized buckling phenomena occurring under edgewise compression of foam-based sandwich panels. Results of parametric FE analyses indicate that, if the total thickness of the sandwich wall is fixed, including thicker facesheets in the laminate yields a larger deflection of the panel that becomes more sensitive to buckling. Furthermore, the mechanical response of the foam sandwich panel is found to be rather insensitive to the level of waviness of core-facesheet interfaces.