Background <p>Sjӧgren’s disease (SjD) is a complex and heterogeneous disease with female predominance. However, gender-related differences in the clinical and immunological profiles of SjD patients have not been fully explored, especially after adjusting for confounding factors such as age and disease duration. This study aims to investigate these gender-specific differences in a Chinese cohort.</p> Objectives <p>To explore the gender-related clinical and immunological differences in patients with SjD by conducting a propensity score-matched (PSM) study, controlling for age and disease duration.</p> Methods <p>We retrospectively evaluated the medical records of patients with SjD who visited Peking University Peoples Hospital between January 2018 and December 2023. Using propensity scores, we matched females and males 1:1 based on age and disease duration. We then collected various clinical aspects from the medical records and compared them by gender.</p> Results <p>Male patients exhibited distinct clinical and immunological profiles compared to females. Clinically, males had a significantly higher prevalence of smoking (<i>P</i> &lt; 0.001), along with lower frequencies of leukopenia (<i>P</i> &lt; 0.001) and peripheral nervous system involvement (<i>P</i> = 0.039).&#xa0;Immunologically, males showed higher white blood cell counts (<i>P </i>= 0.002), lymphocyte counts&#xa0;(<i>P </i>= 0.033), and neutrophils levels (P=0.037), whereas females had elevated antinuclear antibody&#xa0;levels (<i>P </i>= 0.040) and erythrocyte sedimentation rates (<i>P </i>= 0.008). Furthermore, male patients&#xa0;displayed distinct lymphocyte profiles, characterized by reduced proportions of CD8+ T cells&#xa0;(<i>P </i>= 0.016), but increased natural killer cell counts.</p> Conclusion <p>This study highlights significant gender-related differences in the clinical and immunological features of primary Sjögren’s syndrome in a Chinese cohort. Despite sharing similar sicca symptoms with females, male patients exhibited distinct immunological and hematological profiles. These findings underscore the importance of considering gender when assessing and managing SjD patients in clinical practice.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="justify" colname="c1" colnum="1" /> <colspec align="justify" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> <p><b>Key Points</b></p> <p>• <i>Gender differences in SjD were assessed after adjusting for age and disease duration.</i></p> <p>• <i>Males had less leukopenia and nervous system involvement but similar sicca symptoms.</i></p> <p>• <i>Males showed higher NK cell counts and lower CD8+ T proportions.</i></p> <p>• <i>Shared core symptoms but distinct immune profiles support gender-aware management.</i></p> </entry> </row> </tbody> </tgroup> </Table></p>