OBJECTIVES: Chronic inflammation increases the production of cytokines and activates proinflammatory pathways which may lead to nonspecific low back pain (LBP). We systematically reviewed the literature to investigate whether inflammatory biomarkers are associated with nonspecific LBP. MATERIALS AND METHODS: CINAHL, Medline, and Embase were searched between January 1946 and May 2018. MeSH terms and key words were used to identify studies examining the association between inflammatory biomarkers and LBP. Two reviewers performed the risk of bias assessment and 3 reviewers extracted data independently. Qualitative evidence synthesis was performed. RESULTS: Thirteen studies, ranging from fair to low quality, were included. Five studies examined the association between C-reactive protein (CRP)/high-sensitivity CRP and LBP; 6 studies assessed tumor necrosis factors (TNFs); 8 studies assessed interleukins (ILs); and 2 studies assessed fibrinogen. There was evidence for an association of elevated levels of CRP, TNFs, and IL-6 with LBP. There was conflicting evidence for an association between IL-1β, fibrinogen, and LBP. DISCUSSION: Our findings support the notion of a positive association between inflammatory biomarkers and nonspecific LBP, specifically for CRP, TNFs, and IL-6. Although further high quality longitudinal studies are needed to confirm these findings and evaluate the magnitude of these associations, our findings suggest a role of inflammation in the pathogenesis of nonspecific LBP.