Ｏｂｊｅｃｔｉｖｅ　To investigate the risk factors of respiratory depression and its sensitivity in predicting hypoxemia in painless colonoscopy.　Methods　A total of 120 patients [American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ] who underwent painless colonoscopy from February to March 2018 were enrolled. The patients were divided into a respiratory depression group (group D) and a non-respiratory depression group (group N), according to whether respiratory depression [end-tidal carbon dioxide partial pressure (PETCO2)≥50 mmHg (1 mmHg=0.133 kPa) or disappearance of waveform ≥15 s] was achieved during surgery. The following indicators of both groups were recorded: gender, age, length of examination, propofol doses, body mass index (BMI), obstructive sleep apnea syndrome (OSAS) history, the interval from respiratory depression to hypoxemia [pulse oxygen saturation (SpO2)<90%] and the interval from the onset of hypoxemia alert values to hypoxemia.　Results　Remarkable difference was found in age, BMI, and OSAS history between the two groups, while age and BMI were the independent risk factors for respiratory depression. According to receiver operating characteristic (ROC) curve, age, BMI, and both can predict respiratory depression to some extent. Notably, the area under the ROC curve for both age and BMI was greater, compared with age and BMI alone (P<0.05). Compared with group N, group D had advantages in predicting hypoxemia(P<0.05). Compared with traditional oxygen saturation value (SpO2), monitoring PETCO2 predicted hypoxemia earlier, with earlier respiratory depression (63.9 s) than hypoxemia on average (SpO2<90%).　Conclusions　Patients with older ages and high BMI in painless colonoscopy are more likely to present respiratory depression. Monitoring PETCO2 can be more sensitive to predict the occurrence of hypoxemia, providing sufficient time for our treatment of hypoxemia to guarantee patient safety.