Cytomegalovirus (CMV)-seropositivity has been shown to have a negative effect on influenza vaccine-specific antibody responses. In this paper, we confirm and extend these results showing for the first time, a negative association between CMV-seropositivity and B cell predictive biomarkers of optimal vaccine responses. These biomarkers are switched memory B cells and AID in CpG-stimulated B cell cultures measured before vaccination which positively correlate with the serum response to the influenza vaccine. We also found that CMV-seropositivity is associated with increased levels of B cell-intrinsic inflammation and these both correlate with lower B cell function. Finally, CMV-seropositivity is associated with decreased percentages of individuals responding to the vaccine in both young and elderly individuals.