Psoriasis is a chronic inflammatory skin disease with systemic involvement that might predispose to many psoriasis-related comorbidities, such as metabolic syndrome and cardiovascular disorders. Clusterin (Clu), also known as apolipoprotein J (ApoJ), is a highly conserved disulfide-linked heterodimeric glycoprotein implicated in a great variety of physiological and pathophysiological processes including lipid transportation, tissue remodeling, senescence, cell interaction, stress response, inflammation, apoptosis, diabetes mellitus and metabolic syndrome. Serum levels of Clu were assessed in 15 patients with moderate-to-severe psoriasis defined by the presence of a Psoriasis Area and a Severity Index (PASI) value of 10 or more. It was found that the Clu value was significantly higher in patients than in healthy subjects (p <0.001). Our data confirm that the association of psoriatic disease with some comorbidities, especially metabolic and cardiovascular disease, might support the correlation with increased circulating Clu. In particular, it should be pointed out that, according to the recent literature, the Clu could also have a protective role in the comorbidity of psoriasis patients. In addition, it has been published that Clu protects cardiomyocytes against ischemic cell death and is a potential therapeutic agent in the treatment of myocardial infarction; therefore it can be assumed that an artificial enhancement of Clu in the blood could limit the severity of damage also in respect to skin lesions. Although the increase in serum level of Clu was found in all patients with psoriasis, more studies on a larger cohort of patient samples is necessary to confirm the significance of high serum levels of clusterin/ApoJ and to suggest the use of this glycoprotein as an additional new marker in psoriasis pathogenesis. It could be a possibility to improve the prognosis in patients with psoriasis.