Background Psoriasis is a relapsing dermatologic disease with a complex multifactorial etiology. Accumulating evidence has established the presence of cutaneous steroidogenesis with 11 β-hydroxysteroid dehydrogenase (11βHSD) enzyme being the most important final step of this pathway. This enzyme can control local levels of activated glucocorticoids (GCs) in the skin, which is the key to maintaining healthy skin. Methods This case-control study was conducted to evaluate 11βHSD1 level in psoriasis patients, in both lesional and non-lesional skin, compare it to controls, and correlate its activity with the Psoriasis Area and Severity Index (PASI) and the Perceived Stress Scale (PSS). Results A significant decrease of 11βHSD1 level in psoriasis patients compared to healthy controls was observed. In addition, decreased 11βHSD1 level was observed in lesional compared to non-lesional skin in psoriasis patients. There was no significant correlation between the enzyme levels and PASI score or PSS score in patients with psoriasis. However, the PSS score was negatively correlated with 11βHSD1 level in healthy controls. Further histopathological assessment revealed that lower enzyme levels were associated with greater epidermal acanthosis and inflammation. Conclusion This shows the role of 11βHSD1 in controlling psoriatic inflammation, including the degree of epidermal proliferation, which might reveal the complex symphony of psoriasis pathogenesis.