Abstract Background The aim of this study was to evaluate the endothelial function, systemic inflammatory biomarkers and subgingival microbial profile associations in patients with and without periodontal disease. Methods Forty‐four patients, half with chronic moderate to severe periodontitis (cases) and half gingivitis and incipient periodontitis (controls) were recruited. Anthropometric, clinical, biochemical parameters, endothelial function, subgingival microbiota, and eight plasma biomarkers of cardiovascular disease were assessed in both groups. Results Both groups were comparable in anthropometric parameters, blood pressure, and number of positive metabolic syndrome components. Univariate analyses demonstrated significantly higher plasma levels of E‐selectin (64.5 ± 30.9 vs 43.8 ± 22.2; P = 0.026) and myeloperoxidase ( MPO ) (103 ± 114.5 vs 49.1 ± 35.6; P = 0.032) in cases than controls. In addition, significantly higher levels of E‐selectin, MPO and ICAM ‐1 were found in periodontitis patients after adjustment by age and waist circumference. Red complex microorganisms were more frequently detected by culture and polymerase chain reaction in patients with severe to moderate periodontitis. Conclusions Subgingival red complex bacteria and important cardiovascular risk markers were increased in untreated chronic moderate to severe periodontitis cases. Periodontitis seems to be associated with systemic inflammation that could increase the risk of cardiovascular events. The causal relation between periodontal infections and cardiovascular disease requires further research.