Objective <p>This study aims to analyze CD27 expression in various subsets of CD4+ T cells in peripheral blood, explore the functional characteristics of the CD27+ subsets in regulatory T cells (Tregs) and CD4+ T cells, and assess their immunological alterations in newly diagnosed systemic lupus erythematosus (SLE) patients.</p> Methods <p>Peripheral blood was collected from 34 newly diagnosed, untreated SLE patients and 22 healthy controls. Flow cytometry was used to analyze CD27 expression on T cell subsets, comparing the functional markers between CD27+ and CD27- subsets. CD27 expression on Tregs and total CD4+ T cells in SLE patients and healthy controls were compared. ROC curves were constructed, and areas under the curve (AUCs) was calculated to evaluate the diagnostic value of CD27-related T cell subsets for SLE.</p> Results <p>The proportion of Tregs in the peripheral blood of SLE patients was increased, and CD27 expression was higher in Tregs than in CD4+ T cells in healthy individuals. CD27+ CD4+ T cells exhibited higher CD45RA and lower CD226 expression. CD27+ Tregs showed higher Helios and TIGIT expression and lower CD226 expression. CD27+ cell proportions in both CD4+ T cells and Tregs were significantly reduced in SLE patients. The AUC for CD27-related T cell subsets in diagnosing newly diagnosed SLE ranged from 0.6238 to 0.86.</p> Conclusion <p>CD27⁺ CD4⁺ T cells show reduced activation features, while CD27⁺ Tregs exhibit enhanced regulatory potential. Their decreased proportions in SLE patients suggest early immune dysregulation.</p>