<p>Acne vulgaris is a chronic inflammatory skin disease. Recent evidence suggests that systemic immune and metabolic factors, including the kynurenine pathway of tryptophan metabolism, may contribute to its pathogenesis. This study aimed to investigate serum levels of kynurenine pathway metabolites in acne vulgaris. This case-control study included 50 patients with acne vulgaris and 50 age- and sex-matched healthy controls. Serum levels of tryptophan, kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and kynurenic acid were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The kynurenine/tryptophan ratio was calculated as an indicator of indoleamine 2,3-dioxygenase (IDO) activity. Disease severity was assessed using the Global Acne Grading System. Serum levels of kynurenine, 3-hydroxykynurenine, and the kynurenine/tryptophan ratio were significantly higher in the patient group compared to controls, while tryptophan levels were significantly lower. The kynurenine/tryptophan ratio and kynurenine level demonstrated high discriminatory power in ROC curve analysis, with AUC values of 0.904 (95% CI: 0.845–0.962) and 0.896 (95% CI: 0.835–0.957), respectively. Positive correlations were found between kynurenine, the kynurenine/tryptophan ratio, and serum glucose levels. This study reveals altered kynurenine pathway metabolism in patients with acne vulgaris, characterized by increased IDO activity. These findings indicate an association between acne vulgaris and systemic alterations in kynurenine pathway metabolism, warranting validation in larger and comparative cohorts.</p>