Memory consolidation is a dynamic process. Reconsolidation theory assumes that reactivation during wakefulness transiently destabilizes memories, requiring them to reconsolidate in order to persist. Memory reactivation also occurs during slow-wave sleep (SWS) and is assumed to underlie the consolidating effect of sleep. Here, we tested whether the same principle of transient destabilization applies to memory reactivation during SWS. We reactivated memories in humans by presenting associated odor cues either during SWS or wakefulness. Reactivation was followed by an interference task to probe memory stability. As we expected, reactivation during waking destabilized memories. In contrast, reactivation during SWS immediately stabilized memories, thereby directly increasing their resistance to interference. Functional magnetic resonance imaging revealed that reactivation during SWS mainly activated hippocampal and posterior cortical regions, whereas reactivation during wakefulness primarily activated prefrontal cortical areas. Our results show that reactivation of memory serves distinct functions depending on the brain state of wakefulness or sleep.