Major surgery is associated with an increased risk of post-operative immunosuppression and infections. We investigated the influence of influenza vaccination on cell-mediated immune responses in cancer patients undergoing either surgical or conservative therapy. Forty patients with an upper aerodigestive tract tumour were allocated to either a surgical or non-surgical treatment course. Patients within each group were randomized to the vaccination or non-vaccination group. Vaccination was performed twice before surgery or conservative treatment. Human leucocyte antigen receptor (HLA-DR) expression on monocytes was analysed by flow cytometry. In the surgical patients, HLA-DR expression on day 1 after surgery decreased in both the vaccinated and non-vaccinated groups. Vaccinated non-surgical patients showed significantly increased HLA-DR expression levels compared with the non-vaccinated patients. This pilot study demonstrated that vaccination increased monocyte HLA-DR expression in conservatively-treated cancer patients whereas surgery abrogated this response. Vaccination before surgery, therefore, might not help to maintain immune reactivity after surgery.