Nurses have a high prevalence of musculoskeletal symptoms from patient handling tasks such as lifting, transferring, and repositioning. Comorbidities such as musculoskeletal symptoms may negatively affect engagement in leisure-time physical activity (LTPA). However, limited data are available on the relationship between musculoskeletal symptoms and LTPA among nurses. The purpose of this study was to describe musculoskeletal symptoms and LTPA, and to examine the relationships of musculoskeletal symptoms, sociodemographics, and body mass index with LTPA among nurses. Cross-sectional data on sociodemographics, employment characteristics, musculoskeletal symptoms, body mass index, and LTPA were collected from a statewide random sample of 454 California nurses from January to July 2013. Descriptive statistics, bivariate and multiple logistic regressions were performed. We observed that non-White nurses were less likely to engage in regular aerobic physical activity than White nurses (odds ratio [OR] = 0.61; 95% confidence interval [CI] = [0.40, 0.94]). Currently working nurses were less likely to engage in regular aerobic physical activity than their counterparts (OR = 0.48; 95% CI = [0.25, 0.91]). Nurses with higher body mass index were less likely to perform regular aerobic physical activity (OR = 0.93; 95% CI = [0.89, 0.97]) or muscle-strengthening physical activity (OR = 0.92; 95% CI = [0.88, 0.96]). This study found no evidence that musculoskeletal symptoms may interfere with regular engagement in LTPA. Physical activity promotion interventions should address employment-related barriers, and particularly target racial minority nurses and those who have a high body mass index.