Objective: Leptin, the product of the ob gene, plays a key role in a feedback loop that maintains energy balance by signaling the state of energy stores to the brain and by influencing the regulation of appetite and energy metabolism. Zinc also plays an important role in appetite regulation. Thus, we evaluated the relationship between zinc status and the leptin system in humans.Methods: We studied nine healthy men with marginal zinc deficiency, induced by dietary means, before and after zinc supplementation.Results: Zinc restriction decreased leptin levels while zinc supplementation of zinc-depleted subjects increased circulating leptin levels. In addition, zinc supplementation increased IL-2 and TNF-α production that could be responsible for the observed increase in leptin concentrations.Conclusions: Zinc may influence serum leptin levels, possibly by increasing the production of IL-2 and TNF-α.