To assess the relationship between endothelial dysfunction and serum cytokines, anti-SSA and anti-SSB antibodies, beta-2 microglobulin levels, focus score and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in primary Sjögren's syndrome (pSS) patients. The study included 90 patients with pSS and 45 healthy subjects, matched for age and gender, as controls. Serum beta-2 microglobulin, total cholesterol, HDL-cholesterol, triglycerides, TNF-α, and IL-6 were analyzed in both the groups. Patients with pSS were also tested for antinuclear antibodies, anti-SAA (anti-Sjögren's syndrome-related antigen A) antibodies, anti-SSB (anti-Sjögren syndrome related antigen B) antibodies, and focus score (the histopathologic one, based on minor salivary gland biopsy). Endothelial dysfunction was assessed by means of flow-mediated dilation (FMD) in the brachial artery. Data are presented as mean ± standard deviation. Statistical analysis was performed using the -test and the Pearson's correlation. Differences were considered to be statistically significant if the value of < 0.05. Endothelial dysfunction was identified in pSS patients ( < 0.00001). The serum levels of cytokines (TNF-α, respective IL-6) and beta-2 microglobulin were increased in pSS patients compared with controls ( < 0.00001). Endothelial dysfunction (expressed as FMD%) was correlated with focus score, ESSDAI, levels of anti-SSA and anti-SSB antibodies, beta-2 microglobulin, IL-6, and TNF-α, with statistical significance. Endothelial dysfunction is present in pSS patients and is associated with a high focus score and activity as well as increased concentrations of antibodies, pro-inflammatory cytokines, and beta 2-microglobulin.