Age-matched male and female C57BL/6 mice at 10–12 weeks old were subjected to moderate/severe (65 kdyn) SCI followed by 14 weeks post-injury. (A) Diagram illustrating timepoints by weeks post-injury and behavior experiments conducted after the initial moderate injury. All behavior tests are categorized by the functional outcome that was examined. (B) Weekly BMS scores were recorded to quantify hindlimb locomotor recovery after SCI. Starting from week 4, SCI/Female mice showed significantly higher BMS scores compared to SCI/Male mice (N=10/group, p=0.007). This robust and dramatic difference in recovery rate was persistent until the end of the testing period at week 10. (C-E) Spontaneous activity in an OF apparatus was recorded and analyzed with use of the AnyMaze animal behavior system. Injury effects could be observed in two parameters: total distance travelled and mobility. Sex effects were seen (C) at baseline, (D) after injury, and (C-E) between injury groups. For all tests, N=10/group. **p<0.01, ***p<0.001 vs. Sham group; #p<0.05, ##p<0.01, ###p<0.001 vs. SCI/M group. Two-way ANOVA following Tukey’s multiple comparisons test. Abbreviations: BMS (Basso motor scale), cm (centimeter), FS (forced swim), m (meters), m/s (meters/second), Max (maximum), NSF (novelty suppressed feeding), NOR (novel object recognition), OF (open field), TS (tail suspension), YM (Y-maze).