Background The proposed 2024 McDonald criteria incorporate the kappa free light chain (KFLC) index as an additional biomarker in multiple sclerosis (MS) diagnosis. Emerging evidence suggests that a high KFLC index may relate to worse outcomes in people with MS (pwMS). This study had two main objectives: to evaluate the diagnostic performance of the KFLC index against the 2017 and proposed 2024 clinico-radiological McDonald criteria, and to explore its prognostic significance. Methods We performed a retrospective cohort study of adults with a first episode suggestive of MS (2019–2024). All underwent lumbar puncture with simultaneous determination of the KFLC index and oligoclonal bands (OCB). Results Among 150 participants, OCB showed sensitivities of 85.9% (2017) and 86.6% (2024) with specificities of 79.7% and 81.9%. A KFLC index cut-off of 12.0 yielded sensitivities of 87.5% (2017) and 88.1% (2024) with specificities of 79.2% and 81.4%, comparable to OCB. In pwMS, KFLC index ≥ 100 was associated with younger age (OR 1.53, p = 0.048), women (OR 1.53, p = 0.037), relapses (OR 2.30, p = 0.029) and new infratentorial or spinal cord (SC) lesions (OR 6.90, p = 0.003). In multivariable analysis, KFLC index ≥ 100 remained associated with new infratentorial or SC lesions (aOR 8.07, p = 0.019). Conclusion The KFLC index shows diagnostic utility comparable to OCB; however, it is an adjunctive biomarker that complements clinical and MRI findings and should not be used as a standalone diagnostic test. An elevated KFLC index was associated with short-term accrual of infratentorial or SC lesions; these exploratory findings require validation in larger, longer-term cohorts.