This paper presents an experimental and analytical study to investigate the effect of masonry infill on the seismic performance of special Concentrically Braced Frames (CBFs). Cyclic lateral load tests are conducted on three half-scale specimens including two special CBFs with and without masonry infill and a moment resisting steel frame with masonry infill for comparison purposes. Companion analyses are performed to study the influence of masonry infill on the potential rupture of gusset plates and top-seat angle connections by using detailed FE models validated with experimental results. It is shown that the presence of masonry infill could increase the lateral stiffness and load carrying capacity of the special CBF by 33% and 41%, respectively. However, the interaction between masonry infill and the frame significantly increased the strain demands and failure potential of the connections. The results of the experimental tests and analytical simulations indicate that ignoring the influence of masonry infill in the seismic design process of CBFs results in a premature fracture of the connection weld lines and a significant reduction in the deformation capacity and ductility of the frame. This can adversely influence the seismic performance of the structure under strong earthquakes. The results of this study compare well with the damage observations after the 2003 earthquake in Bam, Iran.