Background: The results of several cross-sectional studies suggested a relationship between periodontitis and higher serum levels of C-reactive protein (CRP). Most of these studies were restricted to adult study groups with severe periodontal inflammation, and the potential effects of confounding factors were frequently overlooked.Methods: A case-referent study comprised of 87 adolescent cases who presented with clinical attachment loss >= 3 mm recorded in >= 2 of 16 teeth and 73 controls who did not fulfill these criteria was nested in a fully enumerated adolescent population. Venous blood samples were obtained, and CRP levels were quantified, using a high-sensitive bead-based flow cytometric assay. The Mann-Whitney U test was used to assess overall differences between groups.Results: The median serum CRP values for cases and controls were 64 ng/ml (interquartile range: 27 to 234 ng/ml) and 55 ng/ml (31 to 183 ng/ml), respectively (P = 0.8).Conclusions: Serum levels of CRP were not significantly higher among subjects with periodontitis than among controls. However, a statistically significant positive association between percentages of sites with bleeding on probing and log-transformed CRP values was observed.