End-stage renal disease (ESRD) patients, including those on hemodialysis, possess a high risk for cardiovascular diseases, as the first leading cause of death among them. Traditional risk factors do not utterly elucidate this. Throughout the last two decades, CD4(+)CD28(null) T cells; an unusual subset of T lymphocytes, was detected high with excess cardiovascular (CV) mortality. We aimed to investigate the circulating CD4(+)CD28(null) T cells frequency in ESRD patients on hemodialysis and to evaluate their relationship with atherosclerotic changes. High resolution carotid ultrasonography was done to assess the common carotid artery intima media thickness in a number of ESRD patients, accordingly patients were selected and subdivided into two groups; 30 with atherosclerosis (mean [SD] age, 51.6 [6.3] years) and 30 without (mean [SD] age, 48.9 [5.5] years). Another 30 healthy individuals (mean [SD] age, 48.5 [6.8] years) were enrolled. Analysis of CD4(+)CD28(null) T-cells frequency by flow-cytometry was performed in all studied subjects. CD4(+)CD28(null) T cell percentage was significantly higher in ESRD patients, (mean [SD], 7.3 [2.7] %) compared to healthy individuals (mean [SD], 3.0 [0.8] %), (p < 0.001). Additionally, the expansion of these unusual T lymphocytes was significantly higher in ESRD patients with atherosclerotic changes (mean [SD], 9.47 [0.75] %) compared to those without atherosclerosis (mean [SD], 5.22 [2.14] %), (p < 0.001). In conclusion circulating CD4(+)CD28(null) T lymphocyte population showed expansion in ESRD patients, and of interest in correlation to preclinical atherosclerotic changes.