Objectives: To examine how type I interferon (IFN-α) relates to vascular and neuronal abnormalities in systemic lupus erythematosus (SLE) and whether vascular dysfunction correlates with neuronal injury. Methods: In this cross‑sectional study of 147 SLE patients (aged 19–59 years) and 84 age‑ and sex‑matched controls, peripheral artery tonometry measured endothelial function (reactive hyperemia index) and arterial stiffness (augmentation index). Serum neurofilament light chain (NFL) and type I IFN levels were assessed using electrochemiluminescence immunoassays. Clinical data and organ damage indices were obtained from research registries. Multiple linear regression adjusted for age and sex evaluated associations. Results: Compared to controls, SLE patients had significantly higher NFL concentrations and increased augmentation index. Patients with elevated IFN‑α had lower reactive hyperemia index and higher augmentation index and NFL levels than those with low IFN‑α. An organ damage index ≥1 was independently associated with increased NFL, whereas vascular function metrics were not associated with NFL. Conclusions: SLE patients with high type I IFN activity exhibited endothelial dysfunction, arterial stiffness and elevated NFL, indicating vascular and neuronal injury. However, vascular function measured by peripheral artery tonometry did not explain the observed neuronal damage, suggesting that multiple pathways contribute to neuronal injury in SLE【363740386463803†L75-L125】.