Selective serotonin reuptake inhibitors (SSRIs) constitute a first-line antidepressant intervention, though the precise cognitive and computational mechanisms that explain treatment response remain elusive. Using week-long SSRI treatment in healthy volunteer participants, we show serotonin enhances the impact of experimentally induced positive affect on learning of novel, and reconsolidation of previously learned, reward associations. Computational modelling indicated these effects are best accounted for by a boost in subjective reward perception during learning, following a positive, but not negative, mood induction. Thus, instead of influencing affect or reward sensitivity directly, SSRIs might amplify an interaction between the two, giving rise to a delayed mood response. We suggest this modulation of affect-learning dynamics may explain the evolution of a gradual mood improvement seen with these agents and provides a novel candidate mechanism for the unfolding of serotonin’s antidepressant effects over time.