The aim of this study was to evaluate health-related quality of life (HR-QOL) in patients with primary Sjögren's syndrome (pSS) using both Short-Form 36 (SF-36) and World Health Organization Quality of Life Assessment-BREF (WHOQOL-BREF) questionnaires and to determine the effects of anxiety and depression on HR-QOL using the Hospital Anxiety-Depression Scale (HADS). In this cross-sectional study, 107 female patients with pSS (mean age 54.10 ± 10.2 years), fulfilling US-European Consensus Criteria and 109 female controls (mean age 53.4 ± 10.9 years) were included. Student's t test, Mann-Whitney U test, and analysis of variance (ANOVA) were used for statistical analysis. P values > 0.05 were accepted as significant. All domains of the SF-36, with the exception of "Vitality", and all domains of the WHOQOL-BREF with the exception of "Environment", were significantly lower in pSS patients compared with healthy controls. In pSS patients having anxiety according to HADS, the scores of all domains of WHOQOL-BREF were significantly lower, and in patients having depression according to HADS, three of four domains of WHOQOL-BREF were significantly lower compared with the rest of the group. However, the scores of two domains of the SF-36, namely "Role-Physical" and "Role-Emotional" domains, were significantly higher in pSS patients having depression according to HADS. We confirmed the presence of impaired HR-QOL in pSS. Whereas the presence of anxiety and/or depression generally showed a negative affect on HR-QOL, interestingly, depression seemed to improve the scores of "Role-Physical" and "Role-Emotional" domains of the SF-36. This surprising finding might be related to adaptation to changing health. Social support based upon cultural traditions might also have contributed.