Chronic cytomegalovirus (CMV) infection may contribute significantly to T-cell immunosenescence, chronic inflammation, and adverse health outcomes in older adults. Recent studies suggest detectable CMV DNA in peripheral monocytes as a better indicator for this persistent viral infection than anti-CMV IgG serology. Here, we conducted longitudinal comparisons of anti-CMV IgG titers, CMV DNA in the peripheral monocytes, serum IL-6 levels, and CMV pp65 (NLV)-specific CD8+ T-cell frequencies in fifteen community-dwelling older women with twelve year follow-up. The results showed that anti-CMV IgG titers did not change over twelve years. Women with detectable CMV DNA had significantly higher IL-6 levels than those without, both at baseline (3.06 ± 0.58 vs 1.19 ± 0.37 pg/ml, respectively, p < .001) and at the follow-up (3.23 ± 0.66 versus 0.98 ± 0.37 pg/ml, respectively, p < .001). In addition, CMV pp65 (NLV)-specific CD8+ T cells were detected only in women who had CMV DNA with similar frequencies at both time points. These findings indicate that anti-CMV IgG serology is neither sensitive to change nor useful for monitoring chronic CMV infection over time. They also provide a basis for further investigation into chronic CMV infection as defined by detectable CMV DNA in the peripheral monocytes and its impact on immunity and health in the elderly.