Background: Acne vulgaris (AV) is an inflammatory skin lesion affecting the pilosebaceous unit. Interleukin-19 (IL-19) is a pro-inflammatory cytokine produced by epithelial cells. C-reactive protein (CRP) level was found to be increased in AV when there is extensive local inflammation. Aim: Estimation of serum level of IL-19 and CRP in AV patients, comparing them with healthy controls (HC). Patients and Methods: This case control study was conducted on 4 groups, group 1 included patients with mild AV, group 2 included patients with moderate AV, group 3 included patients with severe AV, and group 4 included HC matched in age and sex. AV assessment was carried out by using the Global acne grading system (GAGS). Assessment of serum CRP level and serum IL-19 ‎was conducted by using ELIZA. Results: There was a significant difference between both groups regarding serum IL-19 and CRP (P<0.05) with increasing levels of AV patients. There was no significant correlation between the severity groups of AV and age, sex, duration (years), body mass index (BMI) (kg/m²), and CRP. The mean IL-19 level was highest in the severe group (58.22). There was a significant correlation between IL-19 and GAGS score. Regarding the validity of IL-19 and CRP for predicting severe acne vulgaris from mild and moderate acne vulgaris, IL-19 showed higher accuracy (84.85%) compared to CRP (63.64%). Conclusion: Serum levels of IL-19 and CRP are increased in AV and correlated with the disease severity. IL-19 showed higher accuracy compared to CRP in discriminating mild from severe cases.