Psoriasis is a chronic inflammatory process associated with an increased risk of cardiovascular risk factors. sCD40L has been suggested to have a possible role in the pathogenesis, of psoriasis and is known to be associated with inflammation, atherogenesis and cardiovascular events. This study investigated cardiovascular risk factors (sCD40L and homocysteine) as well as subclinical atherosclerosis indicators in psoriatic patients and control subjects. The study included 56 consecutive patients with chronic plaque-type psoriasis and 53 age and gender matched healthy controls admitted to a university hospital. Serum sCD40L and homocysteine levels were measured by ELISA. Carotid artery intima-media thickness and brachial artery flow mediated dilatation (FMD) measurements were determined ultrasonographically. Subjects who had a history of cardiovascular diseases and cardiovascular risk factors and receiving any systemic treatment were excluded from the study. Plasma sCD40L levels were significantly higher in psoriasis patients compared with healthy controls (1.33 ± 0.72 vs. 0.98 ± 0.70 ng/ml P = 0.012), whereas plasma homocysteine levels did not differ significantly between the two groups. FMD was significantly reduced in the psoriasis group compared to the controls (3.83 ± 5.03 vs. 8.45 ± 7.27% P = 0.0001). Multiple linear regression analyses indicated a significant association between psoriasis, sCD40L, and FMD. Psoriatic patients had higher sCD40L levels than healthy controls, which may lead to an increase in cardiovascular diseases. sCD40L may be a more reliable and early predictive marker of cardiovascular events in psoriatic patients. New treatment options that will be developed over sCD40L will benefit in prevention of psoriasis and its cardiovascular comorbidities.