Background: It is still debatable whether psoriasis increases cardiovascular risk indirectly since it is associated with metabolic syndrome or is an independent cardiovascular risk factor. The aim of this study was to evaluate psoriasis severity as an independent predictor of insulin resistance (IR) irrespective of the presence of metabolic syndrome (MetS). Methods: This was a case control study including 128 patients stratified into two groups: patients with psoriasis and metabolic syndrome vs. patients with psoriasis and no metabolic syndrome. MetS was diagnosed according to ATP III criteria with homeostatic model assessment of insulin resistance (HOMA-IR), as well as a homeostatic model assessment of beta cell function (HOMA-β) were calculated. Results: Compared to subjects without metabolic syndrome, patients with metabolic syndrome had a significantly higher Psoriasis Area Severity Index (PASI) values (p < 0.001). The strongest correlation was established for HOMA-IR and the PASI index (p < 0.001), even after adjustment for body mass index (BMI) in regression analysis model. In patients without MetS and severe forms of disease, the HOMA-IR and HOMA-β values were significantly higher compared to mild forms of disease (p < 0.001 for all) while in subjects with MetS no difference was established for HOMA-IR or HOMA-β based on disease severity. Conclusions: Psoriasis severity is an independent risk factor of HOMA-IR, the strongest association being present in the non-MetS group, who still had preserved beta cell function suggesting direct promotion of atherosclerosis via insulin resistance depending on the disease severity, but irrespective of the presence of metabolic syndrome.