Objective To explore the effects of cognitive behavioral therapy (cognitive behavior therapy, CBT) on peripheral proBDNF levels and attentional function in first-episode depressive disorder patients. Methods 64 patients with first-episode depressive disorder who met the enrollment criteria from January 2020 to December 2021 were included as the study subjects. According to the order of enrollment, 32 cases were included to combined group at first, and then 32 cases were included to the control group. The control group received escitalopram treatment alone, and the combined group combinewith CBT at the base ofcontrol group. Precursor of brain-derived neurotrophic factor (proBDNF）in peripheral blood were measured before and after treatment. The 24-item Hamilton Depression Scale (HAMD-24) and the continuous performance test (CPT) were used to measure the level of depression and the attentional function before and after treatment. Differences within and between groups before and after treatment were analyzed by SPSS.Results There was no difference in pre-treatment proBDNF value, HAMD-24 score and CPT score in the 2 groups. After 8 weeks, the proBDNF value and HAMD-24 scores in the combination group were lower than the control group, and the CPT scores (2,3 and 4 digits) were higher than the control group, and were statistically different (P＜0.05)Conclusion Cognitive behavioral therapy can significantly reduce depressive symptoms, reduce proBDNF, and improve attentional function