.....Here, we asked whether CMV also drives immunity towards a senescent profile in healthy young adults. One hundred and fifty-eight individuals (mean ± SD; age 21 ± 3 years, body mass index 22.7 ± 2.7 kg m2) were assessed for CMV serostatus, the numbers/proportions of CD4+ and CD8+ late differentiated/effector memory cells (i.e. CD27-CD28-/CD45RA+), plasma interleukin-6 (IL-6) and antibody responses to an in vivo antigen challenge (half-dose influenza vaccine). Thirty percent (48/158) of participants were CMV+. A higher lymphocyte and CD8+ count (both p < 0.01) and a lower CD4/CD8 ratio (p < 0.03) were observed in CMV+ people. Eight percent (4/58) of CMV+ individuals exhibited a CD4/CD8 ratio <1.0, whereas no CMV- donor showed an inverted ratio (p < 0.001). The numbers of CD4+ and CD8+CD27-CD28-/CD45RA+ cells were ~ fourfold higher in CMV+ people (p < 0.001). Plasma IL-6 was higher in CMV+ donors (p < 0.05) and showed a positive association with the numbers of CD8+CD28- cells (p < 0.03). Finally, there was a significant negative correlation between vaccine-induced antibody responses to the A/Brisbane influenza strain and CMV-specific immunoglobulin G titres (p < 0.05). This reduced vaccination response was associated with greater numbers of total CD8+ and CD4+ and CD8+CD27-CD28-/CD45RA+ cells (p < 0.05). This study observed marked changes in the immune profile of young adults infected with CMV, suggesting that this virus may underlie rudimentary aspects of immunosenescence even in a chronologically young population.