The isolating nature of various COVID-19 mandates may have reduced physical activity (PA) and increased mental health symptomology among individuals with amputation. However, an investigation of mental health across PA levels before and after the onset of COVID-19 among this group has not been conducted. Therefore, the objective of this study was to investigate group differences in depression, anxiety, and post-traumatic stress symptomology among individuals with amputation who reported being physically “active,” “somewhat active,” or “inactivate” before and during the pandemic. Individuals with an amputation at any level (n = 91; 51% female; age = 52.5±15.5) completed an online questionnaire to assess demographic information, PA levels, and mental health throughout the pandemic. Group differences in self-reported PA before and after COVID-19 onset were assessed by the PA Guidelines for Americans recommendations. The Center for Epidemiologic Studies Depression Scale (CES-D), Generalized Anxiety Disorder (GAD-7), and Posttraumatic Stress Disorder Checklist (PCL-5) scales were used to assess group differences in mental health status. Before and after the onset of COVID-19, 33% and 42.9% of respondents reported that they were inactive, respectively. 58.2% of respondents reported decreased PA since the pandemic’s onset. Prior to the pandemic, active individuals reported lower CES-D (14.21 vs. 19.07; Cohen’s d: -0.414), GAD-7 (3.82 vs. 5.47; Cohen’s d: -0.359), and PCL-5 (15.92 vs. 21.03; Cohen’s d: -0.319) scores compared to inactive individuals. After the onset of COVID-19, scores remained lower for active respondents CES-D (12.67 vs. 20.03; Cohen’s d: 0.-669), GAD-7 (3.17 vs. 5.87; Cohen’s d: -0.598), and PCL-5 (13.39 vs. 19.90; Cohen’s d: -0.430). Individuals with amputation reported decreased PA after the onset of COVID-19. Individuals reporting that they were “active” exhibited improved depression and anxiety symptomology scores compared to those reporting that they were “inactive.”