Systemic sclerosis (scleroderma) is a rare connective tissue disease that can affect multiple organ systems. Case reports and small treatment studies suggest that pain is significant in scleroderma, but few data speak of the frequency or impact of pain. This study sought to determine the frequency and impact of pain, symptoms of depression, and social network characteristics on physical functioning and social adjustment in patients with scleroderma. One hundred and forty-two scleroderma patients completed measures of pain, depressive symptoms, social network characteristics, physical functioning, and social adjustment. Sixty-three percent reported at least mild pain and 50% reported at least mild levels of depressive symptomatology. Hierarchical regression analyses revealed that pain, depressive symptoms, and employment status (disabled/unemployed vs. not) were significant, independent predictors of physical functioning, together accounting for 37% of the total variance. Pain was the single strongest predictor of physical function, accounting for 20% of the variance. Depressive symptoms, physical functioning, diversity of social network, and employment status were significant independent predictors of social adjustment, together accounting for 63% of the variance. Depressive symptoms were the single strongest predictor of social adjustment, accounting for 26% of the variance. The effects of pain and physical function on social adjustment became non-significant when depressive symptoms were entered into the model, suggesting that symptoms of depression mediate the effect of pain and physical function on social adjustment. These findings indicate that pain is common in scleroderma and that pain and depressive symptoms are significant determinants of physical functioning and social adjustment, two important components of health-related quality of life. Increased attention to effective management of pain and symptoms of depression in scleroderma will likely lead to improved functioning and quality of life.