Background: Leptin is an essential hormone in the control of energy homeostasis, whose production and action may be altered in patients with lipodystrophy. Leptin synthesis occurs mainly in adipose tissue, therefore it depends on the amount of body fat. This study aimed to assess the abdominal fat of patients with HIV-associated lipodystrophy and its relationship with leptin levels. Methods: Analytical cross-sectional study involving 40 male patients with HIV-associated lipodystrophy. Serum levels of leptin were measured by ELISA, and insulin levels were measured by a chemiluminescence assay. HOMA-IR was used to evaluate insulin resistance: fasting serum insulin (μIU/mL) × (fasting plasma glucose (mmol/L)/22.5). Total body fat was estimated by skinfold measurements and bioimpedance. Patients with mixed lipodystrophy underwent abdominal CT for subcutaneous and visceral fat measurements, and the visceral-to-subcutaneous fat ratio (VSR) was calculated. Spearman correlation was applied for quantitative associations. Measures of central tendency were compared by the t-test or Mann-Whitney test, and analyses of variance were performed by Kruskal-Wallis test. Results: Forty patients, aged between 35 and 74 years, were evaluated: 27 with mixed lipodystrophy, 10 with lipoatrophy, and 3 with lipohypertrophy. Leptin levels correlated significantly with body fat percentage, BMI, and waist circumference, but not with age. Median levels of leptin were lower in patients with lipoatrophy compared to patients with mixed lipodystrophy (p=0.0393). According to CT results, 70,4% of the patients were classified as VSR>1, and 29,6% as VSR≤1. Significant correlations were found between leptin and visceral fat (CT), insulin, and HOMA-IR, but not between leptin and subcutaneous fat (CT). Conclusions: Our preliminary results suggest that body fat, especially the visceral component, remains the central determinant of leptin levels in patients with mixed lipodystrophy. Also, higher levels of leptin seem to be related to insulin resistance in patients with HIV-associated lipodystrophy, regardless of clinical form.