Aim: The objectve of the study was to determine the salivary cortisol concentrations between patients with primary Sjögren's disease (pSjD) and control subjects. The specific objectives of the study were to determine clinical and laboratory parameters, the EULAR Sjögren's syndrome disease activity index (ESSDAI), the psychological profile, the Oral Health-related Quality of Life (OHRQoL) and their correlations. Methods: A total of 34 subjects participated in the cross-sectional study: 17 patients with pSjD and 17 control subjects. The stimulated whole saliva (SWS) was used as a reference for the determination of salivary cortisol concentration (collected between 9 and 10 am to avoid diurnal fluctuations) by enzyme-linked immunosorbent assays (ELISAs). Results: The salivary cortisol concentration showed a statistically significant difference between patients with pSjD and control subjects (4.49±2.88 vs 0.49±0.37; P < 0,001; Student t-test). The area under the curve (AUC) was 100.0% in patients with pSjD (P < 0,001). The cut-off point was set at >1,454. The patients with pSjD had four times higher scores for depression, six times higher scores for anxiety and four times higher scores for stress compared to control subjects (P = 0,048, P < 0,001, P = 0,038; Mann-Whitney U test). The patients with pSjD had statistically significantly poorer QoL (total) compared to the control subjects (P < 0,001, Mann-Whitney U test). Conclusion: Patients with PSjD show impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis compared to control subjects. Determination of salivary cortisol can serve as an additional diagnostic method (rapid and non-invasive) and indicates the need for an additional therapeutic approach (psychological, psychiatric) in patients with pSjD.