Background <p>Overweight and obesity are prevalent modern health issues. It has been suggested that individuals who are overweight or obese are more likely to experience hypoxemia during gastrointestinal endoscopy. Ciprofol has demonstrated advantages over propofol in endoscopic procedures, including lower rates of respiratory depression among normal-weight populations. This study aimed to compare the incidence of hypoxemia between ciprofol and propofol in overweight and obese patients undergoing gastrointestinal endoscopy.</p> Methods <p>A total of 176 patients were randomly assigned to receive either ciprofol or propofol. The primary outcome was the incidence of hypoxemia, defined as pulse oxygen saturation (SpO₂) &lt; 90%. Additional variables recorded included the lowest SpO₂, recovery times, injection pain, and hypotension.</p> Results <p>Although the incidence of hypoxemia (SpO₂ &lt; 90%) was lower in the ciprofol group compared to the propofol group (10.2% vs. 18.2%, <i>p</i> = 0.131), this difference was not statistically significant. Similarly, the incidence of SpO₂ &lt; 95% showed no significant difference between the two groups (34.1% vs. 44.3%, <i>p</i> = 0.165). However, the incidence of injection pain was significantly lower in the ciprofol group (0% vs. 40.9%, <i>p</i> &lt; 0.001), as was the incidence of hypotension (25.0% vs. 42.0%, <i>p</i> = 0.017).</p> Conclusions <p>The findings of this study indicate that ciprofol offers sedation effects comparable to those of propofol, without significantly altering the incidence of hypoxemia in overweight and obese patients undergoing gastrointestinal endoscopy. However, additional evidence is required to validate these findings due to the limitations posed by the sample size.</p> Trial registration <p>The study was registered with the Chinese Clinical Trial Registry at <a href="http://www.chictr.org.cn">www.chictr.org.cn</a> (registration date: July 22nd 2024, registration number: ChiCTR2400087170).</p>