Previous studies show that people with spinal cord injury (SCI) are less likely than the average American to meet physical activity recommendations, and they face more preventable disease as a consequence. If health and fitness professionals are to effectively increase physical activity among people with SCI, a logical first step is to understand some of the variables related to physical activity in this population. The purpose of this study was to examine the relationship between self-efficacy, social support, and physical activity among adults with SCI living in the United States. Previous studies suggest that self-efficacy moderates the relationship between social support and physical activity in other populations. This study hypothesized that the same moderating effect could be found among people with SCI. Fifty-two American adults with SCI took an online survey to measure self-efficacy, social support, and physical activity. Moderated multiple regression analysis showed a significant correlation between self-efficacy and heavy-intensity physical activity. This is consistent with findings from previous studies on other populations. However, self-efficacy did not moderate the relationship between social support and physical activity, so the hypothesis was rejected. Health and fitness professionals should focus on improving clients’ exercise self-efficacy to increase exercise behavior, and future research should use more representative samples and more objective physical activity measures to look again for the potential moderating effect of self-efficacy.