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Background: The development of new biomarkers is essential to improve diagnostic accuracy and guide treatment decisions in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The aim of this study was to investigate the utility of the serum neurofilament light chain (sNfL) level as a marker for disability and response to immunomodulatory treatment in patients with CIDP., Methods: This prospective, single-center, observational study included 38 patients with CIDP: 19 treatment-naive (CIDP-I) patients assessed before and after the initiation of immunomodulatory therapy and 19 stable patients on maintenance immunoglobulins (CIDP-M). Clinical scales (INCAT, I-RODS, MRC-SS and grip strength) were used to assess disability and treatment response. Nerve conduction study data were collected., Results: The median sNfL level (pg/mL) was greater in CIDP-I patients than in CIDP-M patients (23.4 vs. 7.7; p = 0.002). A reduction in sNfL levels was observed in CIDP-I patients after 5 months of immunomodulatory treatment (23.4 vs. 15.0; p = 0.001). sNfL levels were correlated with greater disability as assessed by the INCAT (p = 0.007), I-RODS (p = 0.004), and MRC-SS (p = 0.016) in treatment-naive patients but not in those receiving maintenance therapy. sNfL levels correlated with the average amplitude of the distal compound muscle action potential of the median, ulnar, peroneal and tibial nerves from the most affected limb (p = 0.043)., Conclusions: sNfL levels are significantly reduced in patients with CIDP who respond to immunomodulatory treatment and are positively correlated with disability. These findings highlight the utility of sNfL as a marker of disease activity and treatment response in patients with CIDP., Competing Interests: Declaration of competing interest The authors report no disclosures relevant to the manuscript., (Copyright © 2025 Elsevier B.V. All rights reserved.)