Abstract: According to an old notion, the axis of “brain-gut-skin” plays a significant role in the pathogenesis of acne vulgaris. This study aimed to compare gastrointestinal dysfunction symptoms in patients with different severities of acne vulgaris with their normal counterparts. In this cross-sectional, case-control study, 120 adolescents and young adults were recruited from two teaching dermatological clinics over a one-year period (2012-2013). These participants were 30 normal subjects (controls), 30 patients with mild acne vulgaris, 30 patients with moderate acne vulgaris and 30 patients with severe acne vulgaris. Frequency of gastrointestinal dysfunction symptoms including halitosis, gastric reflux, abdominal bloating, abdominal discomfort, constipation and diarrhea was compared between the controls and the patients. Serum lipids profile was also compared between the patients and the controls. All the four studied groups were matched for their members’ age and sex. Controls and the cases with mild acne vulgaris were comparable in terms of the frequency of gastrointestinal symptoms. Frequencies of abdominal bloating (30% vs. 10%, p = 0.05) and constipation (36.7% vs. 13.3%, p = 0.04) were significantly higher in the group with moderate acne comparing with the controls. They were also significant more frequent in the patients with severe acne comparing with the controls (40%, p = 0.01 and 46.7%, p = 0.01, respectively). Comparing with the controls, serum lipids profile was significantly deranged only in the cases with severe acne vulgaris. This study showed that gastrointestinal dysfunction is associated with moderate-to-sever acne vulgaris. In addition, serum lipids profile may be abnormal only in severe acne vulgaris.