We assessed association between prior cytomegalovirus (CMV) infection, proinflammatory status and effectiveness of the anti-influenza vaccination. We examined 154 individuals during the epidemic season dividing them according to the age, response to the vaccine and the Senieur Protocol (SP). The anti-hemagglutinins (HI), tumour necrosis factor alpha (TNFalpha), interleukin (IL) 1beta, IL6, IL10, ACTH/cortisol axis, anti-CMV antibodies and CD28+CD57- lymphocytes were assessed. Non-responders of both ages we characterised by higher levels of anti-CMV IgG and higher percentages of CD57+CD28- lymphocytes (known to be associated with CMV carrier status) together with increased concentrations of TNFalpha and IL6 and decreased levels of cortisol. The anti-influenza vaccine induced increase in TNFalpha and IL10 in the all non-responders, while cortisol increased only in the young. Concluding, CMV carrier status eliciting elevated proinflammatory potential could contribute to unresponsiveness to the anti-influenza vaccine.