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AbstractAbstract: Background and Aim: Periodontal diseases are the most prevalent diseases of the oral cavity. The objective of this study was to evaluate the association between the salivary cortisol levels with moderate to severe periodontitis in patients referring to Oral Medicine Department of Dental Branch of Islamic Azad University of Tehran. Materials and Methods: This study was case control. Thirty patients with moderate to severe periodontitis were selected as case group and 30 patients were selected as control group. They answered hospital anxiety and depression scale (HAD scale) stress questionnaire. Periodontal indices such as plaque index and pocket probing depth and clinical attachment loss were assessed. Each subject provided a saliva sample of 1ml and the cortisol level was assessed by ELISA method. Both groups were matched regarding confounding variables (age, sex and smoking). Data were analyzed using chi-squared test and using Odds Ratio. Correlation between HAD scale results and salivary cortisol level was assessed using Pearson correlation test. Results: The mean age of case group was 41.77 ± 7.92 and the mean age of control group was 40.73 ± 7.94. Cut off point of salivary cortisol level was determined as 5.7 ng/ml by ROC curve method. There were 17 patients (56.7%) in case group and 4 in control group (13.3%) who exhibited salivary cortisol level over 5.7 ng/ml (p<0.0005). The mean of HAD scale was 14.07 ± 6.10 in case group and 11.27 ± 4.24 in control group. Conclusion: The results indicate that there is a significant positive association between elevated salivary cortisol levels and moderate to severe periodontitis. This finding justifies further cohort studies or clinical trials.