〔Abstract〕 Objective To investigate the expression of dehydroepiandrosterone(DHEA) and melatonin in peripheral blood of patients with acquired premature ejaculation(APE) and their clinical significance. Methods The peripheral blood from 27 APE patients and 30 healthy controls were collected. The expression of DHEA gene and melatonin receptor 1 gene were detected by qPCR. The secretion levels of DHEA and melatonin in serum were analyzed by Elisa. Student'ttest or Mann-Whitney U test was used for comparison between the two groups, and the correlation between the two variables was analyzed by Pearson or Spearman correlation. Results The gene expression of DHEA and melatonin receptor 1 gene in peripheral blood of patients with APE was lower than that of the control group(P<0.01,P<0.01). The serum concentrations of DHEA and melatonin secretion in the premature ejaculation group were lower than those in the control group(P<0.05,P<0.001). Changes in serum melatonin concentration in APE patients were correlated with Chinese Index of Sexual Function for Premature Ejaculation-5(CIPE-5) score, which was statistically significant(r=0.773 8,P<0.05). Conclusion The expression of DHEA and melatonin significantly decrease in APE patients. Melatonin is associated with disease severity.