Metallothionein (MT) is a small molecular weight protein possessing metal binding and free radical scavenging properties. We hypothesized that MT-1/MT-2 null (MT^-/-) mice would display exacerbated soleus muscle atrophy, oxidative injury, and contractile dysfunction compared to the response of wild-type (WT) mice following acute spinal cord transection (SCT). Four groups of mice were studied: Wild-type laminectomy (WT lami), wild-type transection (WT trans), MT^-/- laminectomy (MT^-/- lami), and MT^-/- transection (MT^-/- trans). Laminectomy animals served as surgical controls. Mice in SCT groups experienced similar percent body mass (BM) losses at seven days post-injury. Soleus muscle mass (MM) and MM:BM ratio were lower at seven days post-injury in SCT vs. laminectomy mice, with no differences observed between strains. However, soleus muscles from MT^-/- trans mice showed reduced maximal specific tension (sP_o) compared to MT^-/- lami animals. Mean cross-sectional area (μm²) of Type I and Type IIa fibers decreased similarly in SCT groups compared to laminectomy controls and no difference in fiber distribution was observed. Lipid peroxidation (4-hydroxynoneal) was greater in MT^-/- trans vs. MT^-/- lami mice but protein oxidation (protein carbonyls) was not altered by MT deficiency or SCT. Expression of key antioxidant proteins (catalase, manganese and copper-zinc superoxide dismutase) was similar between the groups. In summary, MT deficiency did not impact soleus muscle mass loss but resulted in contractile dysfunction and increased lipid peroxidation following acute SCT. These findings suggest a role of MT in mediating protective adaptations in skeletal muscle following disuse mediated by spinal cord injury.