Objective Studies on the role of psychosocial vulnerability in the development of arthritis must be performed early in the disease course to exclude the reverse explanation that arthritis leads to psychological symptoms. Therefore, the objective of this study was to investigate the longitudinal (5-year) association between depressive mood, daily stressors, avoidance coping and social support as predictors, and the development of arthritis and other clinical parameters as outcomes, in persons with seropositive arthralgia at risk of developing rheumatoid arthritis. Methods Five-year follow-up data of 231 patients from the Reade seropositive arthralgia cohort were used. Clinical and psychological data were collected using physical examinations and questionnaires. Mixed models and Cox regression analyses were used to assess the 5-year associations between depressive mood, daily stressors, avoidance coping or social support, and the development of arthritis or clinical parameters (tender joint count, Visual Analogue Scale (VAS) pain, VAS morning stiffness and erythrocyte sedimentation rate (ESR)). Results Higher scores for depressive mood and lower scores for social support were not associated with the development of arthritis nor with ESR. However, they were longitudinally associated with an increase in pain (p<0.001), morning stiffness (p<0.01) and tender joint count (p<0.001). No consistent associations were found between daily stressors, avoidance coping and the development of arthritis or other clinical parameters. Conclusion Although an effect on the development of arthritis could not be demonstrated, a strong longitudinal association was found between high depressive mood, low social support and clinical parameters. In persons with seropositive arthralgia, depressive symptoms and low social support may increase musculoskeletal symptoms.