Background: Acne vulgaris (AV) is a sebaceous gland condition caused by a wide variety of underlying causes. A major contributor to this illness is the body's abnormal and too abundant production of sebum. Overactive sebaceous glands or increased sensitivity to normal levels of androgen hormones are the root causes of sebum production. Neurocutaneous nerves express the newly discovered zinc-dependent neuropeptide NEP (NEP). Multiple unpleasant stimuli, both internal and external, have been linked to this expression. Allergy contact dermatitis, atopic dermatitis, psoriasis, and atopic vitiligo (AV) all have a common pathogenetic factor: neuropeptides.Aim: to determine how serum NEP levels in acne vulgaris patients relate to overall health and well-being (HRQoL).Subjects and Methods:Fifty patients with acne vulgaris and fifty controls of similar age and gender participated in this case-control study. Between February 2022 and July 2022, they were scouted from the outpatient clinic of the Dermatology, Venereology, and Andrology Department at Benha University Hospitals. The blood NEP concentration was measured using a commercially available, research-use only Enzyme-Linked Immunosorbent Assay (ELISA) kit for human neprilysin. All patients' HRQoL was evaluated with the use of the dermatological life quality index (DLQI).Results: There was no statistically significant difference in age, sex, or body mass index between the patients and the control group. Acne vulgaris patients had a substantially elevated serum NEP level compared to controls. Patients with mild acne had lower serum NEP levels than those with severe acne. Using ROC analysis, we find that NEP may be a predictor of acne vulgaris. There was a link between NEP and HRQoL.Conclusion: Patients with AV had considerably greater serum NEP levels compared to controls. Acne vulgaris patients may experience a decline in quality of life due to this increase. To verify these findings, larger-scale investigations are required.