Background: Immunological disease-related chronic cerebrospinal venous insufficiency (CCSVI) is rarely reported. This study aimed to analyze clinical characteristics, inflammation, and coagulation status in patients with immunological disease-related CCSVI. Methods: Patients with CCSVI were enrolled from 2017 to 2019 and divided into three cohorts based on their immunological disease backgrounds, including groups with confirmed autoimmune disease, with suspected/subclinical autoimmune disease, and with non-immunological etiology. Immunological, inflammatory, and thrombophilia biomarker assay in blood samples were obtained. Mann-Whitney U test or Fisher's exact test was used to compare continuous variables or categorical variables between the CCSVI patients with or without the immunological etiology. Spearman correlation analysis was conducted among age, baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), interleukin-6 (IL-6), C-reactive protein (CRP), and neuron-specific enolase (NSE) in the three groups. Results: A total of 255 consecutive patients with CCSVI were enrolled, including three subgroups: CCSVI with confirmed autoimmune disease (n=41), CCSVI with suspected/subclinical autoimmune disease (n=116) and CCSVI with non-immunological etiology (n=98). In the first subgroup, a series of 41 cases was confirmed with eight different autoimmune diseases including antiphospholipid syndrome (n=18), Sjogren's syndrome (n=8), immunoglobulin G4-related disease (n=7), Behcet's disease (n=2), autoimmune hepatitis (n=2), Wegener's granulomatosis (n=2), systemic sclerosis (n=1) and AQP4 antibody-positive neuromyelitis optica spectrum disorder (n=1). Groups with immunological etiology did not show a higher incidence of thrombophilia or increased proinflammatory biomarkers (e.g., neutrophil, IL-6). However, patients with non-immunological etiology had a higher baseline level of CRP. Additionally, baseline PLR was moderately correlated to NLR and CRP in CCSVI patients with non-immunological etiology and suspected/subclinical autoimmune disease. Conclusions: The formation of CCSVI may be based on the inflammatory process, facilitated by multiple risk factors, among which medical history of immunological diseases may play a significant role due to the intricate relationship between inflammation and coagulation. Moreover, CCSVI may also cause an independent inflammatory injury in venous walls, leading to focal stenosis or thrombus, without attacks from autoimmune antibodies.