Background: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. The cardinal pathogenic factors include increased sebum secretion, follicular hyperkeratinization and microbial colonization by Cutibacterium acnes. Calprotectin is released from activated neutrophils, and can be detected in serum or other body fluids. Aim: The aim of the present study was to clarify if calprotectin plays a role in acne vulgaris pathogenesis. Subject and Methods: This study is a case control study included 42 patients complaining of acne vulgaris compared with42 apparent healthy individuals matching in age and sex with control group. Human calprotectin level in the serum was measured using enzyme linked immunosorbent assay (ELISA). Results: The results showed that serum calprotectin level was higher in patients than controls but the difference was statistically insignificant(P=0.12). However, there was statistically significant correlation between serum calprotectin level in severe acne subtype and mild to moderate subtypes (P=0.026). The patients with acute onset had a higher serum calprotectin level than the patients with gradual onset (P=0.42), the difference was statistically insignificant. The male acne patients had higher statistically significant serum calprotectin level than female patients (P=0.03) Conclusion: Serum calprotectin level was higher in patients with acne vulgaris than controls, and is positively correlated with disease severity, therefore, might help in the evaluation of acne vulgaris severity and can help to evaluate the response to treatment.