Background and Aims. Metabolic syndrome (MetS) has been associated with occurrence and prognosis of ischemic stroke. This study aimed to evaluate whether an association exists between MetS and early neurological deterioration (END) following acute ischemic stroke and the possible role inflammatory biomarkers play.Methods and Results. We conducted a prospective cohort investigation that involved 208 stroke patients within 48 hours from symptom onset. MetS was determined by the modified National Cholesterol Education Program/Adult Treatment Panel III criteria. END was defined as an increase of⩾1 point in motor power or⩾2 points in the total National Institutes of Health Stroke Scale (NIHSS) score within 7 days. Univariate logistic regression analysis showed that patients with MetS had a 125% increased risk of END (OR 2.25; 95% CI 1.71–4.86,P=0.005). After adjustment for fibrinogen and high-sensitivity C-reactive protein, MetS remained significantly correlated to END (OR 2.20; 95% CI 1.10–4.04,P=0.026) with a 77% elevated risk per additional MetS trait (OR 1.77; 95% CI 1.23–2.58,P=0.002).Conclusions. This study demonstrated that MetS may be a potential predictor for END after ischemic stroke, which was independent of raised inflammatory mediators.