Background: Patients with pSS have an increased prevalence of endothelial dysfunction and premature atherosclerosis, and in recent years the focus of research has been on subclinical atherosclerosis in patients with autoimmune diseases. Recently, adropin was discovered, a secretory protein that plays a significant role in the regulation of lipid metabolism and insulin resistance, and also has a positive effect on the function of endothelial cells and has an antiinflammatory effect. Elevated homocysteine levels have been shown to be a strong and independent cardiovascular risk factor in a healthy population. Homocysteine has also been shown to be an independent risk factor for the development of subclinical atherosclerosis. The use of CIMT, a valid marker of generalized atherosclerosis and risk of vascular disease, may help identify high-risk patients with subclinical atherosclerosis. Objective: The aim of this study was to determine the level of adropin and homocysteine and CIMT values in patients with pSS compared to healthy controls. Additional objectives were to investigate the correlation between adropin, homocysteine and CIMT with immunological parameters in pSS as disease-specific antibodies, EULAR Sjögren's syndrome disease activity index (ESSDAI) and Sjögren's syndrome disease damage index (SSDDI). Methods: In this cross-sectional study, 52 patients with pSS and 52 subjects in the control group were included, comparable in terms of age, sex, smoking and BMI. For the homocysteine part of the study, 48 patients with pSS and 46 subjects in the control group were included. Demographic variables and classic cardiovascular risk factors: hypertension, dyslipidemia, obesity and smoking habits were assessed in both groups, and features associated with the disease in the pSS group were also collected through clinical examination and interviews. ESSDAI and SSDDI were used to assess disease activity and chronic disease damage. Enzyme immunoassay (ELISA) was used to analyze adropin. Serum homocysteine concentration was measured using a chemiluminescent microparticle immunoassay (CMIA). The presence of subclinical atherosclerosis was determined by CIMT assessed by carotid ultrasound. Results: Patients with pSS have significantly higher adropin levels compared to controls (3.76 ± 0.68 vs. 3.14 ± 0.69 ng/mL, p < 0.001). Adropin levels in patients with pSS are positively correlated with HDL (r = 0.290, p = 0.036) and anti SSA/Ro52 antibodies (r = 0.307, p = 0.026) and negatively correlated with SSDDI (r = −0.401, p = 0.003). Multivariate linear regression showed that adropin levels were independently associated with HDL (β ± SE, 0.903 ± 0.283, p = 0.002) and SSDDI (β ± SE, -0.202 ± 0.073, p = 0.008). 100 Arterial pressure was higher in patients with pSS (p = 0.007) for systolic blood pressure (SBP) and (p = 0.018) for diastolic blood pressure (DBP). Contrary to expectation, total cholesterol (TC) was higher in the control group (p = 0.047). Homocysteine values were significantly higher in patients with pSS (p=0.015), as well as CIMT (p = 0.0372). Homocysteine positively correlated with triglycerides (TG) (r = 0.204, p = 0.048) and CIMT (r= 0.231, p=0.046). CIMT was positively correlated with age (r = 0.416, p < 0.0001), SBP (r=0.293, r=0.004) and with Sjögren's syndrome impairment index (SSDDI) (r = 0.351, p = 0.014). It also negatively correlated with Sjögren's syndrome-specific autoantibodies anti SSA/Ro60 (r = -0.431, p = 0.002) and anti SSB/La (r = -0.346, p = 0.016). Conclusion: Our findings are implying that patients with pSS have an increased risk for subclinical atherosclerosis and that adropin could be involved in the pathophysiology of pSS and the in mentioned processes by acting protectively on the endothelium. We also showed that there is a significant association between the subclinical atherosclerotic process and homocysteine. So, homocysteine could be a cheap and available marker for risk stratification of the development of subclinical atherosclerosis in asymptomatic patients. These results suggest that the inclusion of determination of plasma adropin and homocysteine levels in risk reduction protocols may be relevant to identify individuals at higher risk of atherosclerotic events. Ultimately, this would enable timely taking of preventive measures that would reduce the mentioned risks.