Shortly after the report of pandemic 2009 influenza A (H1N1), vaccine manufacturers, in conjunction with public agencies, started developing a H1N1 vaccine. In 2009, various approaches were implemented around the globe. The United States and Australia finally approved only non-adjuvanted H1N1 influenza vaccines, whereas Canada and the EU also approved adjuvanted vaccines. In 2010, seasonal influenza vaccine without adjuvant was again widely accepted in both hemispheres. The addition of adjuvant to the vaccine enhances the immunogenity of the vaccine in the presence of a relatively low amount of antigen. However, it might also induce undesirable non-specific immune response. For this reason, we conducted a prospective observational study to monitor T cell absolute count and H1N1-specific immunogenicity after 2009 and 2010 immunization. Fourteen healthy volunteers received the monovalent H1N1 AS03 adjuvanted influenza vaccine (3.5 μg of H1N1 and squalene-based adjuvant) in October 2009. The immunization was associated with a significant increase in T lymphocyte absolute count (P < 0.0001), reaching abnormal values in 57% of subjects. During this period, none of the subject showed any manifestation of severe viral infection or inflammation. Acute infection by CMV or EBV viruses was also excluded. In October 2010, the same subjects received a seasonal non-adjuvanted influenza vaccine (15 μg of each: H1N1, H3N2, and B-Brisbane). However, after 2010 immunization, no change in T lymphocyte absolute count was observed. H1N1-induced immunogenicity was good for both vaccines. Our results suggest a pronounced non-specific T cell response after AS03-adjuvanted 2009 H1N1 vaccination.