The immunopathogenesis of polycystic ovary syndrome (PCOS) is established. However, the role of CD4 + CD28null in such patients is underinvestigated. Aim The aim of this study was to evaluate and compare CD4 + CD28null T cells in patients with polycystic ovary (PCO) (with high androgen level and with normal androgen level) and non-PCO patients. Patients and methods This study was carried out at Benha University Hospital. It included 100 PCO patients and 50 controls selected from the gynecology and obstetrics outpatient clinics. All included female patients were subjected to history taking and clinical examination. Transvaginal ultrasound was performed to confirm the ultrasonic criteria of PCOS. Hormonal profile included the evaluation of thyroid-stimulating hormone, prolactin, dehydroepiandrostendione-S total testosterone, lipid profile, and fasting blood glucose. Finally, total lymphocytic count, CD4 T cell, and CD4+ CD28null frequency were evaluated. Results Ovarian volume was significantly increased in higher and normal androgen subgroups (11.18±1.31 and 10.53±0.84) when compared with the control group (7.15±1.66). Immunological profile revealed that there was a significant increase in total lymphocyte count and CD4+ CD28null in the study group when compared with the control group. In addition, there was a significant increase in total lymphocyte count and CD4+ CD28null in both higher and lower androgen subgroups when compared with the control group. Finally, there was a significant increase in CD4+ CD28null in higher androgen when compared with lower androgen subgroup (3.15 vs. 2.73, respectively).