Background <p>Observational studies have shown an association between cerebrospinal fluid (CSF) metabolites and low back pain (LBP), but the causal relationship between these factors remains unclear.</p> Methods <p>We performed a two-sample Mendelian randomization (MR) analysis to examine whether there is a causal relationship between CSF metabolites and LBP. We applied several MR methods, including inverse variance weighting, weighted median, MR-Egger, Wald ratio, and MR-PRESSO, to test the causal relationship and conducted a sensitivity analysis to assess the robustness of the results.</p> Results <p>We identified a total of 12 CSF metabolites significantly associated with LBP, of which Bilirubin, 5,6-dihydrothymine, Erythronate, Mannitol/sorbitol, and Butyrate have a potential inhibitory causal effect on LBP risk (<i>p</i> &lt; 0.05). Meanwhile, 2-hydroxyadipate, Gamma-glutamyl-alpha-lysine, Indoleacetate, N-acetylputrescine, Palmitoyl dihydrosphingomyelin, S-methylcysteine, and 2,3-dihydroxy-5-methylthio-4-pentenoate play a causal role in increasing the risk of LBP (<i>p</i> &lt; 0.05). No significant estimates of heterogeneity or pleiotropy were detected.</p> Conclusion <p>Our study emphasizes the causal relationship between CSF metabolites and LBP risk, providing reference for clinical treatment and prognosis of LBP.</p>