The continuous reaction times (CRT) method describes arousal functions. Reaction time instability in a patient with liver disease indicates covert hepatic encephalopathy (cHE). The effects of sleep deprivation are unknown although cirrhosis patients frequently suffer from sleep disorders. The aim of this study was to determine if sleep deprivation influences the CRT test. Eighteen cirrhosis patients and 27 healthy persons were tested when rested and after one night's sleep deprivation. The patients filled out validated sleep quality questionnaires. Seven patients (38%) had unstable reaction times (a CRTindex < 1.9) compatible with cHE. In these patients, the wakefulness improved or normalized their reaction speed and CRTindex (p = 0.01). There was no change in the other patients' reaction speed or stability. Seven patients (38%) reported poor sleep that was not related to their CRT tests before or after the sleep deprivation. In the healthy participants, the sleep deprivation slowed their reaction times by 11% (p < 0.0001) and in 7 persons (25%) destabilized them. The acute sleep deprivation normalized or improved the reaction time stability of the patients with a CRTindex below 1.9 and had no effect in the patients with a CRTindex above 1.9. There was no relation between reported sleep quality and reaction time results. Thus, in cirrhosis patients, sleep disturbances do not lead to 'falsely' slowed and unstable reaction times. In contrast, the acute sleep deprivation slowed and destabilized the reaction times of the healthy participants. This may have negative consequences for decision-making.