Serotonergic involvement has been implicated in preferential consumption of treat foods. We tested the effect of acute tryptophan depletion (ATD) on food consumption by overweight and lean adults with and without a history of recurrent major depressive disorder (MDD). ATD and taste-matched placebo challenges were administered double-blind in counter-balanced order. Participants were classified as lean (n=36) or overweight (n=19) on the basis of body mass index (BMI). Total calorie, carbohydrate, protein, and sweet food consumption were assessed via a test meal 8-h following ATD. Four food items of comparable palatability were offered as a part of the test: two sweet (one carbohydrate-rich, and one protein-rich) and two non-sweet (one carbohydrate-rich, and one protein-rich). As compared to the placebo challenge, ATD significantly increased sweet calorie intake among overweight participants and increased their propensity to consume sweet food first before any other type of food. Lean participants' sweet calorie intake and food preference were unaffected by ATD. Findings suggest serotonergic involvement in the sweet food consumption by overweight individuals.