Background: Acne vulgaris is an inflammatory skin disease which is extremely common. Acne affects around 85% of teenagers, and its effects can persist into adulthood for some. It has been hypothesized that calprotectin plays an inflammatory function in acne vulgaris, and so contributes to its etiopathogenesis. Objective: The aim of the current study was to measure serum calprotectin in patients with acne vulgaris and finds any links between that measure and the severity of the underlying condition. Patients and methods: A total of 45 people with a diagnosis of acne vulgaris and 45 controls of the same age and sex participated in the study. They were selected from the Dermatology, Andrology, and STDs outpatient clinic at Mansoura University Hospitals between May 2021 and May 2022. Results: Acne vulgaris patients had considerably higher serum calprotectin levels with median of 18.9 compared with a median of 11 of the healthy volunteers (P <0.001). The GAGS (Global Acne Grading System) score was positively correlated with age (r= 0.341, P =0.022), body mass index (r= 0.538, P <0.001), acne duration (r= 0.461, P <0.001), and serum calprotectin (r= 0.874, P <0.001). GAGS scores was also positively correlated with serum calprotectin (r= 0.943, P <0.001), acne duration (r= 0.523, P <0.001), and age (r= 0.392, P =0.008). Conclusion: Acne vulgaris patients had increased serum calprotectin levels compared to control subjects, and they have a statistically significant relationship with disease severity, suggesting that calprotectin may be used as a chemical biomarker to determine disease severity.