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The role of cognitive, social and biological factors in the etiology of chronic periodontitis has been reported. The aim of this study was to evaluate the salivary cortisol level and interleukin-1 B level in patients of Chronic periodontitis in smokers and stress and nonsmokers without stress. The design of study randomized, prospective, double-blinded, and prospective study. The total sample size was comprised of 600 subjects between the ages of 20 and 50 years. The sample size was divided into 300 males and 300 females. Out of 600 subjects, 200 subjects comprised of subjects with chronic periodontitis with positive depression level with a history of smoking (Group I), 200 subjects comprised of subjects with chronic periodontitis without depression and without smoking (Group II), and 200 subjects who were taken as the control group comprised of healthy subjects without chronic periodontitis, without depression level, and no smoking history (Group III). Salivary cortisol levels were determined by enzyme-linked immunosorbent assay (ELISA). The result showed that there was a positive correlation between morning and evening salivary cortisol level in all the groups with correlation coefficient. There was significant higher value of salivary cortisol in Group I patients when compared with Group II and Group III. However, when the comparison of salivary cortisol levels was done between the Group II and Control group, the result showed nonsignificant P value. It is suggested that stress is positively correlated with the salivary cortisol levels in smokers and nonsmokers.