Background: This study aimed to observe the differences in brain gray matter volume in drug-naive female patients after the first episode of major depression with and without stressful life events (SLEs) before the onset of depression.Methods: Forty-three drug-naive female patients voluntarily participated in the present study after the first major depressive episode.The life event scale was used to evaluate the severity of the impact of SLEs during 6 months before the onset of the major depressive episode.High-field magnetic resonance imaging (MRI) scans were obtained, and the VBM and SPM8 software process were used to process and analyze the MRI.Results: Compared to that in patients without SLEs, the volume of brain gray matter was lower in the bilateral temporal lobe, right occipital lobe, and right limbic lobe in the SLE group.However, the gray matter volume did not differ significantly between the two groups after the application of false discovery rate (FDR) correction.Conclusions: Although the results of the present study suggest the absence of significant differences in brain gray matter volume between female drug-naive patients after the first episode of major depression with and without SLEs after FDR correction, the study provides useful information for exploring the definitive role of stress in the onset of depression.