Leptin is pro-inflammatory mediator associated with the pathogenesis of periodontitis. The objective of the current study was to assess the levels of leptin in serum and gingival crevicular fluid (GCF) in chronic periodontitis (CP) patients. This cross-sectional study was conducted in Dental Teaching Hospital, Umm Al-Qura University, Makkah, Saudi Arabia. Forty-five individuals participated in this study: 25 with chronic periodontitis patients and 20 periodontally healthy controls. The patients were selected based on the criteria of American Academy of Periodontology using probing depths, bleeding on probing, clinical attachment loss and radiographs. GCF and serum samples were collected to estimate the leptin concentrations using enzyme-linked immunosorbent assay kits. Serum leptin levels were markedly higher in chronic periodontitis patients than in the healthy group (P < 0.00001). Although GCF leptin levels of chronic periodontitis patients were higher than the healthy group but this difference was not statistically significant (P Value = 0.5198). In conclusion, these results indicate positive association between serum leptin concentrations and chronic periodontitis. However, there was no significant correlation between GCF leptin level and periodontitis. Further studies are required to confirm these finding.