Acne vulgaris is a chronic inflammatory disease affecting the pilosebaceous glands. It primarily manifests on the face, chest, and back, and is prevalent among adolescents of both genders. The mechanism behind it is significantly associated with the inflammatory response triggered by microbial infections and the infiltration of immune cells. However, the precise causal role of immune cells in acne vulgaris is unclear. To this end, we conducted a 2-sample Mendelian randomization analysis to evaluate the relationship between immune cells and the likelihood of developing acne vulgaris. Instrumental variables were chosen from single nucleotide polymorphisms linked to immune cells, as determined by an extensive genome-wide association study. To explore the potential causal relationship between the 731 immune cell traits and the risk of acne vulgaris, we performed a Mendelian randomization analysis using an inverse variance weighting approach. Moreover, sensitivity, heterogeneity and pleiotropy analyses were performed to ensure the reliability of the findings. In addition, a Finnish dataset was used to validate the results of the forward Mendelian randomization analysis and further multivariate Mendelian randomization analyses were performed. Our study identified 31 immune phenotypes causally associated with acne vulgaris. After validation using the FinnGen database, 3 types of immune cells were identified as being associated with the development of acne vulgaris, including secreting regulatory T (Treg) AC (odds ratio [OR] = 0.967, 95% confidence interval [CI] = 0.946-0.989, P = .004), TD DN(CD4- CD8-) %T cells (OR = 1.079, 95% CI = 1.012-1.149, P = .018), CD25 on CD39+ secreting Treg (OR = 0.951, 95% CI = 0.912-0.992, P = .022). Furthermore, multivariate Mendelian randomization analysis revealed that only 1 immune cell, secreting Treg AC, was causally associated with acne vulgaris. This research established a causal link between Treg cells and acne vulgaris, potentially serving as a predictive marker for diagnosing acne vulgaris and advancing new immunotherapy approaches.