The escalating prevalence of metabolic disorders in individuals with long-standing spinal cord injury (SCI) highlights the urgent need for early interventions for prevention and improving quality of life. Individuals with SCI, while often relatively young, are at high risk for developing insulin resistance and type 2 diabetes soon after the onset of injury. Skeletal muscle is the major site of dietary glucose disposal, yet the relationship between adaptations in skeletal muscle after SCI and the development of metabolic disturbances remains poorly understood. Within 6 months after SCI, lower limb muscles atrophy by up to 45% and individuals show a 3-fold increase in intramuscular fat levels compared to able-bodied (AB) controls. Moreover, within 6 months after SCI, fatigue-resistant and oxidative Type I and Type IIa muscle fibers transform into highly fatigable, glycolytic Type IIax and IIx muscle fibers with impaired oxidative metabolism. The maintenance of adequate muscle mass and metabolic function has never been targeted as a potential strategy to prevent chronic metabolic disorders in individuals with SCI. Early prevention of these deleterious adaptations is expected to be more effective than attempting to reverse changes several months or years after SCI.