Spinal pain problems increase with age, but already 21% of Finnish young adults suffer from a musculoskeletal disorder. Chronic widespread pain (CWP) significantly increases one's disability level and up to 50% of people experiencing chronic pain report symptoms of depression. Diagnosing pain is challenging, as it is a subjective feeling and current clinical pain descriptors are not accurate enough to determine pain perception. In this study, variation in the human plasma proteome was investigated with untargeted Mass Spectrometry in young adult twins with weekly chronic multisite spinal pain (n=94), twins with weekly chronic local neck pain (n=99), and healthy twin individuals (n=236). The association of depression with pain and sex-specific proteins in the studied associations was also investigated. The main data analysis approach included multiple regressions which were done with Generalized Linear Mixed Models (GLMM). Of the 411 studied proteins, Aldolase B and Angiotensinogen were negatively associated with weekly chronic concomitant neck and back pain in men. These proteins are known to relate to muscle atrophy and might thus contribute to the development of musculoskeletal pain. In addition, individuals with weekly chronic concomitant neck and back pain had more symptoms of depression than individuals with weekly chronic local neck pain. Further research is needed to identify the key proteins for clinical settings and upcoming pain proteomics research should include both women and men to examine sex differences.