Background: TNF-α, an adipokine involved in systemic inflammation and a member of a group of cytokines that stimulate the acute phase reaction, has been related to the pathogenesis of both periodontitis and obesity. The objective of this study was to assess the serum levels of adiponectin, leptin and TNF-α of periodontally healthy normal weight (NW) patients, NW patients with chronic periodontitis (CP), periodontally healthy obese patients and obese patients with CP. Material and Methods: Ninety-three patients were enrolled in this cross-sectional study: 30 periodontally healthy NW patients; 18 NW patients with CP; 21 periodontally healthy obese patients; and 24 obese patients with CP. Analyses included clinical and anthropometric outcomes, as well as the assessment of serum levels of adiponectin, leptin and TNF-α by enzyme linked immunosorbent assay (ELISA) or fully automated chemiluminescence immunoassay. One-Way ANOVA, Kruskal-Wallis One-Way on Ranks, Dunn’s Test and multivariable logistic regression (MLR) analyses were conducted to estimate the degree of association between periodontitis and obesity. Results: Obese patients with CP showed significant more bleeding sites than the other three groups ( p <0.05). Moreover, patients from the NWCP and OPH showed similar BOP percentages, as well as OPH group showed more bleeding sites than the NWPH group ( p <0.05). The OPH group showed similar levels of adiponectin and leptin than the OCP group, but significantly higher than the NWPH and NWCP groups( p <0.05). MLR analyses showed that obesity was positively associated with the percentage of sites with bleeding on probing, with an odds ratio of 0.93 (95% confidence interval: -0.88, - 0.98; p =0.012). Conclusions: The serum levels of adiponectin, leptin and TNF-α were not influenced by CP. Obese patients showed almost 10% more sites with BoP. In chronic periodontitis patients, obese subjects presented significant more BOP sites than normal weight subjects