Sleep electroencephalographic (EEG) slow-wave activity is increased after wakefulness and decreases during sleep. Regional sleep EEG differences are thought to be a consequence of activation of specific cortical neuronal circuits during waking. We investigated the relationship between handedness and interhemispheric brain asymmetry. Bilateral EEG recordings were obtained from the frontal and occipital cortex in rats with a clear paw preference in a food-reaching task (right, n = 5; left, n = 5). While still naïve to the task, no waking or sleep EEG asymmetry was present. During the food-reaching task, the waking EEG showed significant, substantial power increases in the frontal hemisphere contralateral to the dominant paw in the low theta range (4.5-6.0 Hz). Moreover, the non-REM sleep EEG following feeding bouts was markedly asymmetric, with significantly higher power in the hemisphere contralateral to the preferred paw in frequencies >1.5 Hz. No asymmetry was evident in the occipital EEG. Correlation analyses revealed a positive association between the hemispheric asymmetry during sleep and the degree of preferred use of the contralateral paw during waking in frequencies <9.0 Hz. Our findings show that handedness is reflected in specific, regional EEG asymmetry during sleep. Neuronal activity induced by preferential use of a particular forelimb led to a local enhancement of EEG power in frequencies within the delta and sigma ranges, supporting the hypothesis of use-dependent local sleep regulation. We conclude that inherent laterality is manifested when animals are exposed to complex behavioral tasks, and sleep plays a role in consolidating the hemispheric dominance of the brain.