Aim: This cross-sectional study was repeated at two time points and investigated the influence of gingivitis, smoking and body mass index (BMI) on the systemic inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL6) in 10- and 15-year-olds. Materials and Methods: The study sample of two birth cohorts, i.e. GINIplus and LISAplus, from the Munich centre consisted of 806 and 846 subjects who were evaluated at 10- and 15-year follow-ups respectively. Children and their parents completed questionnaires on participant-related lifestyle information. Gingivitis was measured at the sextant level using a simplified sulcus-bleeding index. Serum hs-CRP and IL6 levels were obtained from blood samples. Multiple logistic regressions adjusting for lifestyle-related factors and other confounders were performed to assess associations between the specified variables. Results: There were no associations between gingivitis and the inflammatory markers hs-CRP and IL6 in 10-year-olds. In 15-year-olds, gingivitis (aOR: 2.17; 95% CI: 1.25-3.77); daily smoking (aOR: 6.27; 95% CI: 1.39-28.39); and being overweight/obese (aOR: 4.95; 95% CI: 0.73-33.68) were identified as significantly influencing factors for elevated hs-CRP values. Oral hygiene did not influence hs-CRP. Conclusion: In this study, hs-CRP was positively associated with gingivitis, smoking daily and overweight/obesity among 15-year-olds.