Asymmetrically supported and loaded sandwich panels with a polyurethane soft core and isotropic or orthotropic steel faces were analyzed in laboratory tests and numerical simulations. The influence of the steel face microprofilation on the mechanical and kinematical responses of the sandwich panel is considered in the paper. The real experiments were conducted for two supporting systems. For each supporting system isotropic and orthotropic sandwich faces were taken into account. The numerical simulations, in which 2D composite shell elements were used, correspond to the real experiments. The laboratory tests showed that introducing the orthotropic face layer significantly increases the load capacity of the sandwich panel. In the case of asymmetrically supported systems effective flexural rigidity increases too. The paper demonstrates that a relatively simple FE model can be successfully used to assess the global behavior of sandwich panels in complex boundary conditions. Satisfactory consistency of the numerical and real results in the linear range of structural behavior was obtained. Further improvement of the model is possible by introducing a definition of the failure criteria.