AbstractIntroductionLipocalin‐2 (LCN2) is an acute‐phase protein that could mediate neuroinflammation after brain injury. We aimed to evaluate if LCN2 level was associated with early neurological deterioration (END) in acute ischemic stroke patients, thus hindering clinical recovery.MethodsWe conducted a prospective study of acute ischemic stroke patients between June 2021 and February 2022. Serum LCN2 concentration was measured after admission using an enzyme‐linked immunosorbent assay. Outcomes included END and 90‐day poor functional outcome (modified Rankin Scale 3‐6). The National Institutes of Health Stroke Scale increment ≥4 points within 72 h after admission was defined as END.ResultsA total of 253 acute ischemic stroke patients (mean age, 65.2 ± 13.4 years; 64.0% male) were recruited. In the multivariate adjustment, increased serum LCN2 levels (per 1‐SD increase of LCN2) were associated with a higher risk of END (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.20–2.25;p= .002) and 90‐day poor outcome (OR, 1.73; 95% CI, 1.22–2.45;p= .002). Restricted cubic splines found a linear relationship between LCN2 level and 90‐day unfavorable outcome (END,p= .001 for linearity; 90‐day poor outcome,p= .013 for linearity). Subgroup analysis further confirmed the significant association of LCN2 with clinical outcomes.ConclusionsThis study demonstrated that higher circulating LCN2 level was associated with an increased risk of early clinical worsening and 90‐day unfavorable outcomes in ischemic stroke patients.