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Sleep hyperhidrosis is defined as profuse nocturnal sweating that disrupts sleep. Although the mechanism is unknown, some cases are secondary to hot flushes during the menopausal period, medical, mental and sleep disorders, and medication, while dysregulation of thermoregulation during sleep is suspected in primary cases. We present the case of a woman with severe primary sleep hyperhidrosis, occurring nightly for 23 years, which definitively resolved after brief treatment with oxybutynin (a muscarinic receptor-blocking anticholinergic). An ammoniacal odor in the sweat and a sensation of coldness on awakening during sweating episodes suggest that the mechanism of her night sweating was not an exacerbation of thermoregulation during the night but shares the mechanical properties of emotional/psychological sweating. This extreme case of sleep hyperhidrosis was treated with excellent efficacy and minimal side effects using oxybutynin, which could benefit other patients with nighttime discomfort., Citation: Dias L, Martinot C, Vaillant G, Arnulf I. Severe night sweating treated by oxybutynin. J Clin Sleep Med . 2024;20(1):169-172., (© 2024 American Academy of Sleep Medicine.)