This study employs data-driven approaches to analyze single-cell transcriptomic differences between male and female subjects in subpopulations of peripheral blood mononuclear cells (PBMCs). Applying a RandomForestRegressor, we observed consistent model performance across different samples. We reveal significant sex differences in PBMC subpopulations, most notably in four cell types: CD4+ Th2, CD8+ naïve T, CD4+ memory Treg, and CD4+ Th1/17 cells.