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Background/Aims The aetiology of primary chronic pain syndromes (CPS) is highly disputed. One theory suggests that pain is due to a pro-inflammatory cytokine milieu leading to nociceptive activation. We performed a systematic review and meta-analysis aiming to assess differences in cytokines levels in CPS patients versus healthy controls (HC). Methods Human studies published in English from PubMed, MEDLINE/Scopus and Cochrane databases were searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with cytokine measurements in CPS patients and HC. We excluded studies with underlying organic pathology. Quality assessment was completed using a modified version of the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. Study registered with PROSPERO (CRD42020193774). Results Initial search yielded 324 papers, 36 studies (3229 participants) eligible for systematic review and 26 studies (2048 participants) suitable for metaanalysis. There were reproducible findings supporting trends of cytokine levels comparing CPS patients with HC. Eotaxin (chemokine) however was consistently raised in CPS. Meta-analysis showed significantly increased tumour necrosis factor (TNF) (SMD=0.39, p = 0.0009, %95I=0.16-0.63, p < 0.001; I2=70%, Q2 p < 0.001), interleukin (IL)-6 (SMD=0.15, 8 (SMD=0.26, p = 0.01, 95%CI =0.05-0.47; I2=61%, Q2 p = 0.005) and IL-10 (SMD=0.61; %95 = 0.34-0.89, p < 0.001; I2 = 10%, Q2 p = 0.34) in CPS compared to HC. Conclusion We found significant differences in peripheral blood cytokine profiles of CPS patients compared to HC. However, the distinctive profile associated with CPS includes both pro-inflammatory (TNF-α, IL-6, IL-8), and anti-inflammatory cytokines (IL-10) in pooled analysis, as well as chemokine (eotaxin) signatures. Disclosure L. Furtado O'Mahony: None. A. Srivastava: None. P. Mehta: None. C. Ciurtin: None.