BACKGROUND: The aim of this study was to evaluate plasma levels of soluble receptor activator of nuclear factor-kappa B ligand (sRANKL) and osteoprotegerin (OPG) in smoker versus non-smoker chronic periodontitis patients. METHODS: Plasma samples were obtained from 13 smoker and 31 non-smoker systemically healthy chronic periodontitis patients, as well as 13 smoker and 29 non-smoker systemically and periodontally healthy subjects. Before commencing any periodontal intervention, venous blood samples were obtained and whole-mouth clinical periodontal measurements were recorded. sRANKL and OPG concentrations in plasma samples were determined by enzyme-linked immunosorbent assay (ELISA) technique. Data were tested statistically by student's t test, Wilcoxon matched pairs test, and Spearman's correlation analysis. RESULTS: All clinical periodontal measurements were significantly higher in chronic periodontitis groups than the healthy controls (p < 0.05). Smoker and non-smoker chronic periodontitis patients exhibited similar values in all clinical periodontal measurements and plasma sRANKL, OPG concentrations (p > 0.05). Smoker chronic periodontitis patients exhibited significantly lower (p = 0.007) plasma OPG concentrations and higher sRANKL/OPG ratio (p = 0.01) than smoker healthy controls. CONCLUSIONS: Within the limits of this study, periodontal inflammation in smoker chronic periodontitis patients seems to lower plasma osteoprotegerin levels and thereby increase the RANKL/OPG ratio, and possibly play a role in the increased susceptibility for alveolar bone destruction in smoker subjects.