Aims: The initial phase of multiple sclerosis (MS), often known as clinically isolated syndrome (CIS), is a critical period for identifying individuals at high risk of progressing to full-blown MS and initiating timely treatment. In this study, we aimed to evaluate the prognostic value of CXCL13 and IL-8 as potential markers for CIS patients’ conversion to MS. Methods: Our study encompassed patients with CIS, those with relapsing-remitting MS (RRMS), and control subjects, with sample analysis conducted on both cerebrospinal fluid (CSF) and serum. Patients were categorized into four groups: CIS-CIS (no MS development within two years), CIS-RRMS (conversion to RRMS within two years), RRMS (already diagnosed), and a control group (CG) with non-inflammatory CNS disorders. Results: Results showed significantly elevated levels of CXCL13 in CSF across all patient groups compared to the CG (p < 0.0001, Kruskal-Wallis test). Although CXCL13 concentrations were slightly higher in the CIS-RRMS group, statistical significance was not reached. Similarly, significantly higher levels of IL-8 were detected in CSF samples from all patient groups compared to the CG (p < 0.0001, Kruskal-Wallis test), with comparable levels among patient groups. ROC analysis in the CIS-RRMS group identified both CXCL13 (AUC = 0.959) and IL-8 (AUC = 0.939) in CSF as significant predictors of CIS to RRMS conversion. Conclusion: In conclusion, our study suggests a trend toward elevated CXCL13 levels in CIS patients progressing to RRMS. These findings emphasize the importance of identifying prognostic markers to guide appropriate treatment strategies for individuals in the early stages of MS.