Objective To investigate the prevalence and risk factors of isolated nocturnal oxygen desaturation (INOD) in pre-discharge inpatients with chronic obstructive pulmonary disease (COPD). Methods Totally 431 inpatients with COPD in this department were screened during January to June in 2017, in which pre-discharge inpatients without daytime hypoxia were enrolled in this study. Portable and wearable oximeter was used to record whole night oxygen saturation, pulse, hand movement of the inpatients within two days before being discharged. The clinical characters and symptoms, resting daytime artery gas analysis results, spirometry results, Epworth Sleepiness Score (ESS), Pittsburgh Sleep Quality Index (PSQI) were recorded and compared between INOD and non-INOD patients. Moreover, these data were furtherly compared between patients with or without suspected COPD-SAHS overlap syndrome (OS) to reveal the differences in clinical features. Logistics regression was used to find out independent predictors. Results One hundred and six pre-discharge inpatients without daytime hypoxia were screened out and out of them, 44 patients (41.5%) were proven with INOD. Patients with INOD presented lower daytime SaO2 [(91.8±1.1)% vs. (94.4±1.5)%, P<0.05], moreover, the patients with suspected OS had a higher yearly exacerbation frequency (2.1±0.6 per yearvs. 1.4±0.4 per year, P<0.05), higher ESS score (10.5±2.7vs. 5.1±2.5, P<0.05) and PSQI (12.8±4.4vs. 7.4±3.1, P<0.05). Conclusions Even in pre-discharge COPD inpatients without daytime hypoxia, there is 41.5% of them suffering from unrevealed INOD. Lower daytime oxygen saturation and higher ESS indicate probable INOD and with higher exacerbation risk in OS patients. To screen out INOD in pre-discharge COPD is of clinical value and in need of attention.