Abstract Four individuals with a spinal cord injury underwent 16 weeks of isometric electrical stimulation training to both legs for 60 min, five times per week during the first 5 months after injury, while two SCI individuals remained untrained. A baseline biopsy sample of the vastus lateralis muscle was obtained within 1 month of injury, and another biopsy sample was taken after a further 16 weeks. The untrained, paralyzed skeletal muscle displayed a reduction in (1) type I fibers (from 50% to 9%), (2) myosin heavy chain (MHC) I (from 27% to 6%), and (3) fiber cross-sectional area of type I, type IIA and type IIX fibers (−62%, −68%, and −55%, respectively) when compared to the baseline sample of muscle taken within 1 month of injury. In contrast, the trained group showed smaller alterations in type I fibers (from 49% to 40%) and MHC I composition (from 39% to 25%), while fiber cross-sectional area was similar to baseline levels for type I, type IIA and type IIX fibers (−3%, −8%, and −4%, respectively). In conclusion, electrical stimulation training can largely prevent the adverse effects of a spinal cord injury upon paralyzed human skeletal muscle if applied soon after the injury.