Serotonin (5-HT) has long been implicated in social behavior and impulsivity, but the mechanisms through which it modulates self-control remain unclear. We observed the effects of manipulating 5-HT function on behavior in the ultimatum game, where players must decide whether to accept or reject fair or unfair monetary offers from another player. Participants with depleted 5-HT levels rejected a greater proportion of unfair offers, but not fair offers, without showing changes in mood, fairness judgment, basic reward processing, or response inhibition. Our results suggest that 5-HT plays a critical role in regulating emotion during social decision-making.