Context: The psychosocial stress has long been regarded as a significant pre-disposing factor for periodontal disease. The association between the periodontal disease and the neuroendocrine hormones has been observed. Chromogranin A (CgA) is supposed to link the activity of the neuroendocrine system to local and systemic immune functions and to be related to periodontitis. Aims: The aim of this study was to determine the CgA levels in saliva and plasma in periodontal health and disease and to assess their potential relationship to periodontitis. Settings and Designs: In this case-control study, the association between periodontal disease and stress marker has been assessed. Materials and Methods: Sixty subjects were chosen for this study: With case group comprising of 30 subjects with chronic periodontitis and control group comprising of 30 healthy subjects. Salivary and plasma CgA levels were determined by ELISA technique. Clinical parameters included were plaque index, papillary bleeding index and clinical attachment loss and probing depth. Correlation analysis was calculated by independent sample t-test. Results: Significantly higher CgA levels were found in saliva and plasma of patients with chronic periodontitis compared with healthy individuals (P < 0.05). No significant difference were observed between salivary and plasma CgA levels. Conclusions: The elevated level CgA in the plasma and saliva of subjects with stress induced chronic periodontitis has yielded insights into biological plausible association between the psychosocial stress and chronic periodontitis. Thus, our results suggest that CgA is a useful biomarker for evaluating at least in part the etiopathogenesis of periodontitis.