Background: Staphylococcus aureus, the major virulence factor of hospital and community acquired infections, secretes numerous exotoxins (super antigens), which may affect immunological and inflammatory status in psoriatic skin lesion.Objectives: This study is designed to compare the S. aureus super antigens level in sera of psoriatic patients with normal cases (nevus).Patients and Methods: A case control study was performed in dermatology ward of Rasoul Hospital in Tehran, IR Iran (2008 - 2010). Staphylococcal super antigens (Entrotoxin A, B, D and TSST1) were measured in serum of 41 psoriatic patients and 28 normal persons (Nevus) by ELISA. Chi square values (CI 95%, P value<0.05) were calculated for all categorical variables.Results: In this study 63.4% (26) of cases were male, 36.6% (15) were female. Age ranged from 4 months to 64 years old, with a mean age of 33.7±15.4 years. Type of skin disease in cases: 20% (8) were inflicted by the Gutate form of the disease; 59% (23) with chronic plaque psoriasis (CPP), 7.7% (3) with erythrodermic and 12.8% (5) had other types of the disease (plaque, pustular, inverse). TSST (toxic shock syndrome toxin) was detected in 47% (20.41) of cases and in 6% (1.28) of the controls with a significant difference. (P value=0.000) Entrotoxins (A, B, D) were detected in the sera of 48.8% (21.41) of cases; and only 6 % (1.21) of controls, showed significant differences (P value=0.000) positive TSST was more common in spring, and correlates with CPP type of psoriasis, but not related to patient’s gender and age.Conclusions: In this study, S. aureus were 25 times more in psoriatic patients. Super antigens should be first detected in the serum samples; if negative, the skin lesions should be examined by PCR especially in chronic types of disease. Adding the antibiotics against S. aureus to other conventional treatments might be helpful. It has a more important and significant role in children with acuteinfection.