Overall, 55 sural nerve biopsies from patients with CIDP (n=36) and CIDP-variants (n=18) were included into the study. Immunohistochemical analysis of the sural nerve specimens showed an aberrant deposition of terminal complement complex C5b-9 on endoneural capillaries in 52 (94%) of patients in addition to endoneural CD8+ T cell- and CD68+ macrophage infiltration. Gene expression studies showed an increase of factors C3 and C6 compared to NDCs with no difference in regard to clinical phenotype, whereas levels of IL6 or TNF-alpha were not significantly elevated. Our proteomic profiling approach revealed the statistically significant dysregulation of 50 proteins, which based on their respective functions suggest altered mitochondrial activity, perturbed cytoskeleton, and increased oxidative stress. The majority of patients with high to moderate complement deposition presented with a progressive disease course, however without any correlation with disease severity as measured by INCAT or MRC at baseline and follow-up. Our combined data supports the role of complement in CIDP pathogenesis. Based on these findings, we propose to further evaluate complement inhibition therapies as new targeted treatment option for patients with CIDP.