Background: Psoriasis is a common chronic immune mediated papulosquamous disease. Its prevalence around 2-3% of the general population,and is characterized by an exaggerated proliferation of keratinocytes secondary to an activated immune system. Objective: the aim of this work was to investigate the relationship between serum Calprotectin and psoriasis vulgaris and to correlate with disease severity. Patients and Methods: the present study was conducted on 50 patients with psoriasis (group A) and 30 healthy control subjects (group B). Both groups were subjected to full history taking, clinical examination and estimation of serum level of calprotectin using ELISA technique. PASI score was used to assess disease severity in group A. Results: calprotectin level was significantly higher in cases group than in control group. A positive statistical correlation between the calprotectin level and the disease severity (PASI score) was observed but not with age, sex, nor duration of disease. Conclusion: calprotectin can be used as a marker of psoriasis severity and progression. Calprotectin may play a role in the pathogenesis of psoriasis.