Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and exerts antidepressant effects, which has been considered to be mediated by increasing serotonin concentration in the inter-synaptic cleft. However, the monoamine hypothesis has not been fully supported as there is a time lag between transient increases in brain serotonin levels after SSRI treatment and the expression of antidepressant effects. The temporal inconsistency may be partly reconciled by memory mechanisms, especially in the hippocampus. A theory of memory suggests that learned memory needs to be consolidated into neuronal circuits by repeated reactivation of memory-encoding neuronal activity. Our previous study demonstrated that the inhibition of the ventral hippocampus after stress experiences inhibits subsequent depression-like behavior in mice. Especially, we found that sharp wave ripples (SWRs), which represent synchronized neuronal spikes in the ventral hippocampus, are a primary neuronal activity pattern to mediate this effect. Here, we tested whether fluoxetine affects SWRs in the ventral hippocampus in resting and depression model mice and found that fluoxetine administration significantly reduced ventral hippocampal SWRs in both resting mice and mice that received social defeat stress. These results demonstrate that fluoxetine inhibits SWR-induced neuronal reactivation, suggesting an antidepressant effect mediated by suppressing memory consolidation.