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OBJECTIVE Slow waves are thought to mediate an overall reduction in synaptic strength during sleep. The specific contribution of the thalamus to this so-called synaptic renormalization is unknown. Thalamic stroke is associated with daytime sleepiness, along with changes to sleep electroencephalography and cognition making it a unique "experiment of nature" to assess the relationship between sleep rhythms, synaptic renormalization, and daytime functions. METHODS Sleep was studied by polysomnography and high-density electroencephalography over 17 nights in patients with thalamic (n = 12) and 15 nights in patients with extra-thalamic (n = 11) stroke. Sleep electroencephalography overnight slow wave slope changes, and their relationship with subjective daytime sleepiness, cognition, and other functional tests were assessed. RESULTS Thalamic and extra-thalamic patients did not differ in terms of age, sleep duration or apnea-hypopnea index. Conversely, overnight slope changes were reduced in a large cluster of electrodes in thalamic compared to extra-thalamic stroke patients. This reduction was related to increased daytime sleepiness. No significant differences were found in other functional tests between the two groups. INTERPRETATION In patients with thalamic stroke a reduction in overnight slow wave slope change and increased daytime sleepiness was found. Sleep- and wake-centered mechanisms for this relationship are discussed. Overall, this study suggests a central role of the thalamus in synaptic renormalization. This article is protected by copyright. All rights reserved.