Simple SummaryDamage to the spinal cord affects the voluntary control of skeletal muscles and also the control of the autonomic nervous system, thus affecting the cardiorespiratory system and the magnitude of the impact that is related to the level and complete or incomplete nature of the spinal cord injury. Associated with spinal cord damage are a sedentary lifestyle, increased adipose tissue, and low-grade inflammation/oxidative damage at the systemic level and in the lung. Lung malfunction has been recurrently described in this pathological context in both epidemiological and experimental studies. Physical exercise (PE) seems to be a potential therapeutic strategy, which involves a large mass of muscle tissue, thus potentially improving both lung functionality and the control of systemic and pulmonary inflammation. Furthermore, it is hypothesized that specific PE for the respiratory musculature per se or in association with other general exercise protocols may positively contribute to the function of this tissue.AbstractChronic spinal cord injury affects several respiratory-function-related parameters, such as a decrease in respiratory volumes associated with weakness and a tendency to fibrosis of the perithoracic muscles, a predominance of vagal over sympathetic action inducing airway obstructions, and a difficulty in mobilizing secretions. Altogether, these changes result in both restrictive and obstructive patterns. Moreover, low pulmonary ventilation and reduced cardiovascular system functionality (low venous return and right stroke volume) will hinder adequate alveolar recruitment and low O2diffusion, leading to a drop in peak physical performance. In addition to the functional effects described above, systemic and localized effects on this organ chronically increase oxidative damage and tissue inflammation. This narrative review describes both the deleterious effects of chronic spinal cord injury on the functional effects of the respiratory system as well as the role of oxidative damage/inflammation in this clinical context. In addition, the evidence for the effect of general and respiratory muscular training on the skeletal muscle as a possible preventive and treatment strategy for both functional effects and underlying tissue mechanisms is summarized.