We often experience troubled sleep in a novel environment . This is called the first-night effect (FNE) in human sleep research and has been regarded as a typical sleep disturbance [2-4]. Here, we show that the FNE is a manifestation of one hemisphere being more vigilant than the other as a night watch to monitor unfamiliar surroundings during sleep [5, 6]. Using advanced neuroimaging techniques [7, 8] as well as polysomnography, we found that the temporary sleep disturbance in the first sleep experimental session involves regional interhemispheric asymmetry of sleep depth . The interhemispheric asymmetry of sleep depth associated with the FNE was found in the default-mode network (DMN) involved with spontaneous internal thoughts during wakeful rest [10, 11]. The degree of asymmetry was significantly correlated with the sleep-onset latency, which reflects the degree of difficulty of falling asleep and is a critical measure for the FNE. Furthermore, the hemisphere with reduced sleep depth showed enhanced evoked brain response to deviant external stimuli. Deviant external stimuli detected by the less-sleeping hemisphere caused more arousals and faster behavioral responses than those detected by the other hemisphere. None of these asymmetries were evident during subsequent sleep sessions. These lines of evidence are in accord with the hypothesis that troubled sleep in an unfamiliar environment is an act for survival over an unfamiliar and potentially dangerous environment by keeping one hemisphere partially more vigilant than the other hemisphere as a night watch, which wakes the sleeper up when unfamiliar external signals are detected.