Summary Prolonged disability associated with work-related musculoskeletal disorders, including non-specific low back pain, poses a major and costly problem for the people affected as well as for all of society. The appearance of musculoskeletal disorders and the development of prolonged disability could be related to the presence of stressors that would initiate the activation of physiological mechanisms and the maintenance of an inflammation cycle. The emotional response to these stressors could be the link between the stressors and the activation of the physiological mechanisms. Up to now, few studies have been carried out exploring the possible links between the psychological variables and the physiological mechanisms in the development of prolonged disability. This study is situated in the extension of a previous study on the understanding of determinants of chronic disability (R-253), and its aim was to better understand the phenomenon of prolonged disability in the case of non-specific low back pain by exploring the relationship between certain psychological factors (pain, disability and distress) and the response of the immune and endocrine systems. The results tend to show that there is in fact altered immune and endocrine system function in people suffering from disability for more than three months. However, the authors explain that, based on the results obtained, it is impossible to state that this alteration was caused by the presence of stressors or a negative emotional response. Broader longitudinal studies would be necessary to confirm the existence of a link between these variables—and the nature of this link—and physiological system dysregulation.