Low weight and high strength panels is always a design consideration. Sandwich panel technology offers an efficient solution for this problem. Different types of sandwich panels are currently being used depending on the applications. Honeycomb sandwich panels are a better solution in structural design problem. Different honeycomb cores are currently being used. In the current work, a comparison of response of Square and Hexagonal honeycomb sandwich panels is made. Numerical simulations using FE techniques are used for simulating the behavior of the sandwich panels under uniformly distributed loads. During simulation, two different combinations of materials (face material – core material) are considered. Based on the response, it is found that though Al-Al sandwich panel with square honeycomb structure, though has lower stress values, showed greater deflection than SS-Cu panel. Modal analysis is also executed to extract the natural frequencies. It is found that square honeycomb panel has higher natural frequencies than that of hexagonal honeycomb panel.