Objectives: It has been stated that Sirtuin-6 (SIRT6) play a important role in regulation of inflammation, energy metabolism, homeostasis and apoptosis, and SIRT6 may be assosiciated with many diseases. The aim of this study was to evaluate saliva and serum SIRT6, Lipoxin A4 (LXA4) and Caspase-8 (CASP8) levels in correlation with periodontal clinical status in patients with periodontitis and healthy subjects. Materials and Methods: 20 patients with Stage III Grade B periodontitis (P) and 20 periodontally healthy individuals (control;C) were included in this study. Clinical periodontal parameters were measured. Saliva and serum levels of SIRT6, LXA4 and CASP8 were analyzed by enzyme-linked immunosorbent assay.Results: Serum SIRT6 and saliva LXA4 levels were significantly lower in the periodontitis group than in the control group (respectively; p=0.010, p= p:0.001). There was no statistically significant difference between the periodontitis and control groups for saliva SIRT6, serum LXA4, serum and saliva CASP8 levels (p>0.05). Significant negative correlations were found between all periodontal clinical parameters (PI, BOP, PPD, CAL) and saliva LXA4 level (p<0.05), and between PPD, CAL, and serum SIRT6 level (respectively; r=-0.465 and r=-0.473, p<0.05). Conclusions: This study demonstrated that significantly lower levels of serum SIRT6 and saliva LXA4 in periodontitis patients and their correlation with periodontal status. Detection of SIRT6 and saliva LXA4 might have a potential role for predicting periodontal status in the future with more precise sampling protocols and with better specifity in testing methods. Clinical Relevance: Serum SIRT6 and saliva LXA4 might be promising biomarkers for monitoring the susceptibility to periodontitis and predicting periodontal status.