Background: Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous unit, which affects adolescents and young adults. Interleukin (IL)-23 and IL-17 have been found to significantly influence the chronic inflammatory response. Furthermore, the discovery of their pathways had contributed to a better understanding of the pathomechanism of inflammatory disorders. Objective: This study aimed at measuring serum IL-23 concentrations among AV cases with different severities and to compare them with normal controls. Patients and Methods: This case-control study included 80 subjects who were allocated into 2 groups: Group (A) included 40 cases with acne vulgaris, and group (B) included 40 healthy controls. In the patient group, the Global Acne Grading System Severity (GAGS) was utilized in evaluating the AV severity. Results: The mean serum IL-23 level was statistically significantly greater in the AV group (48.57 ± 17.63 pg/mL) compared to the control group (11.81 ± 4.28 pg/mL). No significant differences were found regarding serum IL-23 concentrations between child versus adult, males versus females, as well as different nutritional status among AV group. There was significant increase in serum IL-23 concentrations with increased severity of AV group (p < 0.001). Conclusion: Serum IL-23 is not only a marker of the pathogenetic process of AV but also it can serve as a prognostic predictor for AV severity.