Major depressive disorder (MDD) is associated with physiological changes commonly observed with increasing age, such as inflammation and impaired immune function. Age-related impaired adaptive immunity is characterized by the loss of naive T-cells and the reciprocal accumulation of memory T-cells together with the loss of T-cell co-stimulatory molecules. Additionally, the presence and activity of cytomegalovirus (CMV) alters the architecture of the T-cell compartment in a manner consistent with premature aging. Because CMV is also thought to reactivate with psychological stress, this study tested whether MDD influences age-related phenotypes of T-cell populations in the context of CMV infection in young and middle-aged adults. Morning blood samples from volunteers with a DSM-IV diagnosis of MDD (n = 98, mean age(SD) = 36(10) years, 74.5% female, 57.1% CMV⁺) and comparison controls (n = 98, mean age(SD) = 34(10) years, 68.4% female, 51.0% CMV⁺) were evaluated for CMV IgG antibody status and the distribution of late differentiated (CD27^-CD28^-) cells within CD4⁺ and CD8⁺ T-cell subsets, i.e. naive (CCR7⁺CD45RA⁺), effector memory (EM, CCR7^-CD45RA^-), central memory (CM, CCR7⁺CD45RA^-) and effector memory cells re-expressing CD45RA (EMRA, CCR7^-CD45RA⁺). Mixed linear regression models controlling for age, sex, ethnicity and flow cytometry batch showed that CMV seropositivity was associated with a reduction in naive T-cells, expansion of EMRA T-cells, and a greater percent distribution of CD27^-CD28^- cells within CD4⁺ and CD8⁺ memory T-cell subsets (p's < 0.004), but there was no significant effect of MDD, nor any significant interaction between CMV and diagnosis. Unexpectedly, depressed men were less likely to be CMV⁺ and depressed women were more likely to be CMV⁺ than sex-matched controls suggesting a possible interaction between sex and MDD on CMV susceptibility, but this three-way interaction did not significantly affect the T-cell subtypes. Our findings suggest that depression in young and middle-aged adults does not prematurely advance aging of the T-cell compartment independently of CMV, but there may be significant sex-specific effects on adaptive immunity that warrant further investigation.