<p>The onset and progression of major depression have been closely linked to the human inflammatory immune system, with T cells playing a crucial role in immune function. Recent studies have highlighted significant associations between changes in T cell-related subpopulations and the onset and progression of major depression. So, the aim of this study was to investigate the relationship between T lymphocyte subset alterations and major depressive disorder (MDD). First, a total of 108 participants were included in this study and were categorized according to the International Classification of Diseases Tenth Revision diagnostic criteria (ICD-10) into four groups: the healthy group (<i>n</i> = 30), the mild depression group (<i>n</i> = 26), the moderate depression group (<i>n</i> = 31), and the major depression group (<i>n</i> = 21). Venous blood samples were collected from all participants, and T cell-related subpopulation markers were analyzed through flow cytometry. Statistical analysis revealed a close link between the CD45⁺ lymphocyte counts and the risk of major depression. Higher levels of CD45⁺ lymphocyte counts were correlated with an increased likelihood of developing major depression. In conclusion, this study identified T cell-related subpopulations, particularly CD45⁺ lymphocyte counts, which are closely associated with the major depression, possibly offering a new avenue for the auxiliary diagnosis of the major depressive disorder.</p>