Insulin resistance, diabetes mellitus, and metabolic syndrome in patients with human immunodeficiency virus (HIV) infection are increasingly being reported in the global medical literature. This cross-sectional study was done to describe the occurrence of metabolic syndrome, diabetes mellitus, and insulin resistance in HIV-positive patients in a tertiary referral center in South India. A total of 60 patients who had HIV infection for 12 months or more were enrolled in the study. Of these, 30 patients were antiretroviral therapy (ART)-naïve, and 30 were treated with ART. Biochemical estimations (fasting blood glucose, 75 g oral glucose tolerance test, lipid profile, and fasting insulin) and anthropometric measurements (height, weight, and waist circumference) were performed for each patient. Metabolic syndrome was diagnosed using National Cholesterol Education Program–Adult Treatment Plan III criteria, and insulin resistance was calculated applying the homeostasis model assessment method. Diabetes mellitus, impaired fasting glycemia, and impaired glucose tolerance were diagnosed based on American Diabetes Association criteria. A high prevalence of metabolic syndrome was observed in patients with HIV (16/60), and was more prevalent in the ART-treated group (13/30; P = 0.028). Similarly, insulin resistance was also noted to be high (24/60), and of these patients, 15 were on ART. Seventy-five percent of patients with metabolic syndrome had insulin resistance. Diabetes was diagnosed in one patient who was ART-naïve and in six patients who were on ART. Our observations suggest an increased prevalence of metabolic syndrome, insulin resistance, and diabetes mellitus in ART-treated patients. These warrant attention and substantiation with larger studies. While ART improves survival, it may lead on to cardiovascular morbidity and mortality, especially in the Indian subcontinent where there is a genetic predisposition to cardiovascular risk