This study investigated the effect of mechanical infection control for periodontitis and periodontal surgery on the prevalence of well-established risk factors for atherosclerosis, and plasma levels of cytokines, antibodies against heat shock proteins and markers of systemic inflammation. Sixty-eight patients between 39 and 73 years of age with severe periodontitis who had been referred to four specialist periodontology clinics in Sweden were investigated. A fasting venous blood sample was taken at baseline and additional samples were collected after 3 and 12 months. A total of 54 patients underwent periodontal treatment. The periodontal treatment was successful, as pathogenic gingival pockets decreased significantly. Plasma glucose, lipids and markers of systemic inflammation were not significantly altered after 3 months. One year after the initial treatment, HDL-C concentrations were significantly increased (Δ0.08 mmol/L) whereas LDL-C concentrations decreased (Δ0.23 mmol/L). Haptoglobin concentrations were also lower. Interleukin-18 and interferon-γ levels were also lower after 12 months (60 ng/L (-23%) and 11 ng/L (-97%) respectively). Treatment had no effect on plasma levels of IgA, IgG1, IgG2 antibodies against heat shock proteins. In conclusion, this study indicates that standard treatment for periodontal disease induces systemic changes in several biochemical markers that reflect the risk for atherosclerosis.