Closed head injury induces cerebral oxidative stress. The efficacy of a Mn (III) porphyrin catalytic antioxidant was assessed in a mouse closed head injury model. Mice were subjected to closed head injury and treated 15 min later with an i.v. bolus of vehicle or 3 mg/kg MnTE-2-PyP5+. Aconitase activity, Fluoro-Jade staining, glial fibrillary acidic protein immunoreactivity, and rotarod falling latencies were measured. Closed head injury altered all variables. MnTE-2-PyP5+ had no effect on any variable with the exception of attenuation of aconitase inactivation at 2 h post-closed head injury. In a second experiment, mice received 3 mg/kg or 6 mg/kg MnTE-2-PyP5+ or vehicle i.v. 15 min post-closed head injury. Rotarod and Morris water maze latencies were measured. Closed head injury altered performance in both tests. No statistically significant effect of MnTE-2-PyP5+ was observed. We conclude that single dose MnTE-2-PyP5+ does not alter outcome in this mouse closed head injury model.