Lower thoracic spinal cord stimulation (SCS) results in the generation of large positive airway pressures. The potential effects of diaphragm co-activation during SCS were investigated in 10 anesthetized dogs. Diaphragm compound action potentials (CMAPs) were present during SCS at the T10 and T12 levels. In group 1, airway (Paw) and trans-diaphragmatic (Pdi) pressures were monitored during supramaximal SCS before and after phrenicotomy. In group 2, pressures were monitored before and after C2 section to evaluate the potential influence of supraspinal centers. Following phrenicotomy in group 1, the reduction in Pdi during SCS was associated with increases in Paw. In group 2, diaphragm CMAPs and active Pdi increased following C2 section, while Paw fell. Following phrenicotomy, Paw increased significantly. In intact animals therefore, changes in Paw during SCS are affected by the interaction between inhibitory and excitatory influences on diaphragm activation. We conclude that lower thoracic SCS results in substantial diaphragm co-activation and secondary reductions in airway pressure generation.