Chronic pain, with its complex and multidimensional nature, poses significant challenges in identifying effective long-term treatments. There is growing scientific interest in how psychopathological and personality dimensions may influence the maintenance and development of chronic pain. This longitudinal study aimed to investigate whether alexithymia can predict the improvement of pain severity following a treatment-as-usual programme for chronic musculoskeletal pain over and above psychological cofactors (emotional distress, catastrophizing, and self-efficacy). A consecutive sample of 129 patients with diagnosed chronic musculoskeletal pain referred to two tertiary care centres was recruited and treated for 16weeks. Clinical pain, psychological distress, self-efficacy, catastrophizing, and alexithymia were assessed with validated self-report measures at the first medical visit (T0) and at 16-week follow-up (T1). Compared with non-responder patients (n=72, 55.8%), those who responded (i.e., reduction of >30% in pain severity; n=57, 44.2%) reported an overall improvement in psychological variables except alexithymia. Alexithymia showed relative stability between baseline and follow-up within the entire sample and remained a significant predictor of treatment outcome even when other predictive cofactors (i.e., pain interference, depressive symptoms, and catastrophizing) were considered simultaneously. Our results suggest that identifying patients with a co-occurrence between alexithymia, depressive symptoms, catastrophizing, and the stressful experience of chronic pain can be clinically relevant in pain prevention and intervention programs.