Co-existent sleep spindles and slow waves have been viewed as a mechanism for offline information processing. Here we explored if the temporal synchronization between slow waves and spindle activity during slow wave sleep (SWS) in humans was modulated by preceding functional activations during pre-sleep learning. We activated differentially the left and right hemisphere before sleep by using a lateralized variant of serial response time task (SRTT) and verified these inter-hemispheric differences by analysing alpha and beta electroencephalographic (EEG) activities during learning. The stability and timing of coupling between positive and negative phases of slow waves and sleep spindle activity during SWS were quantified. Spindle activity was temporally synchronized with both positive (up-state) and negative (down-state) slow half waves. Synchronization of only the fast spindle activity was laterally asymmetric after learning, corresponding to hemisphere-specific activations before sleep. However, the down state was associated with decoupling, whereas the up-state was associated with increased coupling of fast spindle activity over the pre-activated hemisphere. These observations provide original evidence that (1) the temporal grouping of fast spindles by slow waves is a dynamic property of human SWS modulated by functional pre-sleep activation patterns, and (2) fast spindles synchronized by slow waves are functionally distinct.