Persistent pain is considered a complex biopsychosocial phenomenon whose understanding and management is yet to be improved. More research is needed to determine the common paths that lead to developing persistent pain, to identify the populations most at risk and to develop and evaluate interventions. The last decades have seen a shift in pain management, from the biomedical model to a biopsychosocial model. There is also a significant body of evidence emphasizing the effects of osteopathy in persistent pain management. Given the relevance of psychosocial factors in aetiology and maintenance of pain, it is essential to investigate whether osteopathy has an influence on depression, anxiety, fear avoidance or pain catastrophyzing. This review will identify and synthesize relevant primary research focused on the effects of osteopathic interventions on psychosocial factors in patients living with different pain conditions. Studies were identified by searching seven databases (Medline complete, CINAHL, Cochrane Library, Psychinfo, Psycharticles, Web of Science and Scopus) between 1980 and 2017. Peer reviewed articles reporting effects of: Osteopathic manual therapy, Osteopathic Manipulation, Mobilization, Spinal manipulation, high velocity and low amplitude manipulation, massage and soft tissue treatment were extracted. A total of 16 RCTs were selected. Two out of five reported significant differences in depression; in regards to anxiety, all the four trials found significant effects; two out of three trials reported a significant reduction in fear avoidance while six out of seven trials found a significant enhancement of health status and three out of four found an increase in quality of life. The findings of this review are encouraging; suggesting that osteopathic treatment may have some effects on anxiety, fear avoidance, quality of life and general health status in populations living with persistent pain.