Objective　To investigate the relationship between the serum levels of leptin, neuron-specific enolase (NSE) and S-100B in patients of stroke and the incidence of post-stroke depression (PSD). Methods　The clinical data of 121 cases of acute ischemic stroke, admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from Jun. 2010 to Dec. 2012, were retrospectively analyzed. After six months of follow-up 42 patients were diagnosed as suffering from PSD (Hamilton Depression Scale score ≥8). Another 42 participants with available matching data on onset time, age, gender and lesions of brain were selected. The serum samples were collected from all patients at time of discharge, and the concentrations of serum leptin, NSE and S-100B were analyzed by enzyme-linked immunosorbent assay (ELISA) kit. Correlation and efficiency of diagnosing PSD among them was validated by receptor operator curve (ROC). Results　The concentration of serum leptin, NSE, and S-100B in PSD group (25.84±13.80, 2.59±1.48 and 25.0