The purpose of the present study was to determine levels of adipokines and their relationship with stiffness parameters and disease activity index in SLE patients in comparison with healthy controls. Sixty SLE patients and 29 control subjects were enrolled in the study. Serum leptin and adiponectin levels were determined by commercial sandwich ELISA kits. Colour-coded carotid duplex sonography was performed using a Siemens SONOLINE Antares machine equipped with linear 5-13 MHz. SLEDAI, ECLAM and SLICC were evaluated in all patients. Data were analysed by software for statistical analysis (Prism 5.0). Median leptin is higher among SLE patients compared with controls (p 0.035). Median values of vascular stiffness and PSEM are increased in SLE compared with controls (p = 0.0003 and p = 0.007). Vascular strain and vascular distensibility are lower in SLE patients in comparison with controls (p = 0.0001 and p = 0.0006, respectively). Considering SLE patients, leptin levels correlate with vascular stiffness (r = 0.64, p < 0.0001) and PSEM (r = 0.63, p < 0.0001). Adiponectin levels correlate with vascular strain (r = 0.28, p 0.039) and negatively correlate with vascular stiffness (r = -0.38, p 0.039). Leptin levels correlate with disease activity (SLEDAI and ECLAM) and cumulative damage (SLICC) indexes. This study demonstrates higher values of leptin in SLE patients. Moreover, SLE patients show increased levels of vascular stiffness and PSEM and reduced values of vascular strain and distensibility. These results globally indicate a decline in arterial elasticity. We find a positive correlation of leptin with stiffness parameters. According to its atheroprotective action, adiponectin inversely correlates with stiffness parameters.