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Objectives: Transresveratrol (Res) and l-carnitine (l-Car) are proposed to alleviate metabolic and immune disorders and increase physical activity in obese individuals. This study aims to estimate the effect of Res and l-Car in rats with diet-induced obesity., Methods: Male Wistar rats were fed a diet with excess fat and fructose (high-fat high-carbohydrate diet [HFCD]) supplemented with Res and l-Car at doses of 25 and 300 mg/kg of body weight, respectively, for 63 d. An assessment of grip strength, behavioral reactions, as well as biochemical, morphological, and immunological parameters, was performed., Results: Res supplementation did not affect energy consumption, but l-Car increased when animals had free access to feed. Body weight gains were the highest in animals fed the HFCD, lowest in rats receiving the control balanced diet, and intermediate in animals receiving Res and l-Car. Feeding with Res and l-Car canceled the decrease in long-term memory in rats fed the HFCD, as well as reduced anxiety and increased mobility. With both supplements, bilirubin, triglycerides, and low-density lipoprotein levels in the blood plasma returned to normal values, but only l-Car increased the ratio of aspartic and alanine transaminases. In addition, l-Car lowered the levels of leptin and ghrelin and increased transforming growth factor beta 1 in the blood plasma, and consumption of Res was accompanied by a decrease in interleukin-17A and increase in interferon gamma in spleen lysates. Moreover, l-Car reduced the number of cells with lipid inclusions in the liver., Conclusions: The consumption of Res and l-Car leads to a significant reduction in dyslipidemia and inflammation with potentially favorable changes in behavioral responses., (Copyright © 2021 Elsevier Inc. All rights reserved.)