Background: Neuroinflammatory processes have been hypothesized to play a role in the pathogenesis of psychiatric and neurological diseases. Studies on this topic often rely on analysis of inflammatory biomarkers in peripheral blood. Unfortunately, the extent to which these peripheral markers reflect inflammatory processes in the central nervous system (CNS) is unclear. Methods: We performed a systematic review and found 29 studies examining the association between inflammatory marker levels in blood and cerebrospinal (CSF) samples. We performed a random effects meta-analysis of 21 studies (pooled n = 1679 paired samples) that reported the correlation of inflammatory markers in paired blood-CSF samples. Results: A qualitative review revealed moderate to high quality of included studies with the majority of studies reporting no significant correlation of inflammatory markers between paired blood-CSF. Meta-analyses revealed a significant low pooled correlation between peripheral and CSF biomarkers (r = 0.21). Meta-analyses of individual cytokines revealed a significant pooled correlation for IL-6 (r = 0.26) and TNFα (r = 0.3) after excluding outlier studies, but not for other cytokines. Sensitivity analyses showed that correlations were highest among participants with a median age above 50 (r = 0.46) and among autoimmune disorder patients (r = 0.35). Conclusion: This systematic review and meta-analysis revealed poor correlation between peripheral and central inflammatory markers in paired blood-CSF samples, with increased correlations in certain study populations. Based on the current findings, peripheral inflammatory markers are a poor reflection of the neuroinflammatory profile.