© 2019 Elsevier Inc. Purpose: This study tested whether the severity of somatization, panic, generalized anxiety, and depression symptoms mediated relationships between physical activity and pain using structural equation modeling. Methods: College women (n = 1036; mean = SD age of 19.7 ± 3.0 years) reported past week physical activity and the presence of persistent pain (¿1 month). The Psychiatric Diagnostic Screening Questionnaire assessed hypothesized mediators of physical activity effects on pain via symptoms of generalized anxiety, panic, major depressive disorder, and somatization disorder. Results: The percentage of the sample screening positive was 15.7% for generalized anxiety, 5.8% for panic, 11.0% for major depressive, and 16.0% for somatization. The hypothesized model had good fit and accounted for a significant amount of variance in pain (9.1%). Direct paths from physical activity to somatization, generalized anxiety, major depressive disorder, and panic disorder were significant. Paths to pain were significant from somatization and panic disorder. The path from physical activity to pain was not direct but indirect and through significant paths to pain from somatization and panic disorder. Each standard deviation increase in physical activity decreased the probability of pain by 11.0% through panic disorder and 10.7% through somatization disorder. Conclusions: Physical activity is associated with pain indirectly through associations with panic disorder and somatization disorder symptoms in college women.