Aim: The aim of the present study was to explore the associations between periodontal diseases, psycho-neuro-immunologic variables like stress and depression by estimating salivary cortisol (CORT), salivary Chromogranin- A (CgA), and salivary C-reactive protein (CRP). Methodology: A total of 100 patients were included in the study and categorized into two groups which included 50 in control group (healthy individuals) and 50 recall periodontal patients. Psycho-neuro-immunologic variables like stress and depression were assessed through the Derogatis Stress Profile (DSP) and Centre of Epidemiologic Studies Depression scale (CES-D). Periodontal parameters like plaque index, gingival index, probing pocket depth and clinical attachment levels were recorded. Saliva samples were collected for estimation of stress markers such as cortisol, Chromogranin- A, and C-reactive protein. Results: Stress, depression and stress markers were correlated with measures of periodontal disease. In addition, oral care neglect during periods of stress and depression was associated with attachment loss and PD >5 mm. Stress markers and CRP levels were also significantly higher in subjects with stress patients when compared to healthy individuals. Conclusions: The results of our study suggest that stress might be associated with periodontal disease through psychologic and behavioral mechanisms. Our result strengthens the suggested hypothesis of association between psychologic factors and markers of periodontal disease.