Background: Leptin, adiponectin, and resistin may play an important role in the development of lipodystrophy (LD) in HIV/AIDS patients. The aim of this study was to correlate levels of leptin, adiponectin, and resistin between HIV/AIDS patients with LD and without lipodystrophy (non-LD), as well as between subgroups of LD [lipoatrophy (LA), lipohypertrophy (LH), and mixed fat redistribution (MFR)] and non-LD patients. Methods: Cross-sectional study of 66 HIV/AIDS patients. Serum levels of leptin, adiponectin, and resistin were measured. The associations between adipocytokine levels and metabolic variables were estimated by Spearman correlation. Analysis of covariance with bootstrapping method was used to examine the relationship between adiponectin and leptin and lipodystrophy categories. Results: The LD was observed in 29 (44%) patients, while 15 (52%) of them had LA, 4 (14%) had LH, and 10 (34%) patients had MFR. No significant differences regarding leptin, adiponectin, and resistin levels, between LD and non-LD patients, were observed. LH patients had significantly higher levels of leptin and adiponectin in comparison with non-LD patients (P = 0.039, P = 0.011, respectively). Within the LD group, LA patients had significantly lower levels of leptin (LA vs. LH, P = 0.020; LA vs. MFR, P = 0.027), while LH patients had significantly higher levels of adiponectin (LH vs. LA, P = 0.027; LH vs. MFR, P = 0.028). Correlation of adiponectin with LD remains significant in the LH subgroup after adjustment for age, body mass index, cystatin-C, plasminogen activator inhibitor-1 (PAI-1), and interferon gamma (IFN-gamma) (P = 0.001). Conclusions: Adiponectin and leptin levels differ significantly between LH patients and non-LD patients, as well as between the LD subgroups. Adiponectin may be a more useful marker of LD in HIV/AIDS patients.