Patients with systemic autoimmune disease are predisposed to developing sarcopenia associated with their underlying proinflammatory condition and a decrease in motility. How sarcopenic status affects disease progression remains unknown. The present study explored the influence of sarcopenia on immune homeostasis and investigated related biological pathways that might be important for future disease management. A denervation-induced skeletal muscle loss model was established and the function of the immune system was evaluated. The results of immune status profiling and functional assessment demonstrated that the loss of skeletal muscle impaired the function of mitochondrial respiration and activation in T cells, and therefore influenced the balance of T helper cell subsets. Consequently, sarcopenia might promote the progression of autoimmune diseases, such as lupus nephritis, as well as the enhancement of Th1/Th17 functions. These results suggest that physicians should be aware of the impact of the loss of skeletal muscle on the management of autoimmune disease, and that a multidisciplinary approach is required to minimize the overall adverse impact of sarcopenia.