The results from an experimental and analytical study of a composite sandwich fuselage side panel for a transport aircraft are presented. The panel has two window cutouts and three frames, and has been evaluated with internal pressure loads that generate biaxial tension loading conditions. Design limit load and design ultimate load tests have been performed on the graphite-epoxy sandwich panel with the middleframe removed to demonstrate the suitability of this two-frame design for supporting the prescribed biaxial loading conditions with twice the initial frame spacing of 20 inches. The two-frame panel was damaged by cutting a notch that originates at the edge of a cutout and extends in the panel hoop direction through the window-belt area. This panel with a notch was tested in a combined-load condition to demonstrate the structural damage tolerance at the design limit load condition. The two panel configurations successfully satisfied all design load requirements in the experimental part of the study, and the three-frame and two-frame panel responses are fully explained by the analysis results. The results of this study suggest that there is potential for using sandwich structural concepts with greater than the usual 20-in.-wide frame spacing to further reduce aircraft fuselage structural weight.