Guillain-Barré syndrome (GBS) is a common peripheral neuropathy with relatively heterogenous clinical manifestations. In severe cases, it can result in disabling neuromuscular symptoms and respiratory failure. In this study, we assessed whether the systemic immune-inflammation index (SII) is associated with respiratory failure in GBS patients.We retrospectively analyzed clinicopathological data from GBS patients diagnosed in the First Affiliated Hospital of Kunming Medical University. SII was calculated based on counts of neutrophils (N), platelets (P), and lymphocytes (L). Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values for SII, N, P, and L. Univariate and multivariate logistic regression were performed to determine the ability of the SII to predict respiratory failure.Among the 369 GBS patients in this study, 61 (16.5%) suffered respiratory failure. Multivariate logistic regression showed that N ≥ 6.03 × 109/l, Hughes Functional Grading Scale (HFGS) score ≥ 3 at admission, and SII ≥ 863.04 × 109/l can independently predict respiratory failure in GBS patients. SII showed higher predictive ability than N, based on area under the ROC curve (0.75 vs. 0.72).SII may be a novel independent prognostic indicator of respiratory failure in GBS patients, helping physicians identify those at risk in a timely manner.