Background <p>Oxygen saturation imaging endoscopy is a system that maps oxygen saturation (StO₂) in real time using endoscopy noninvasively. This study aimed to objectively evaluate StO₂ in colorectal polyps using oxygen saturation imaging endoscopy.</p> Methods <p>We examined 133 colorectal lesions, including 78 adenomas (ADs), 35 hyperplastic polyps (HPs), and 20 sessile serrated lesions (SSLs). Prior to endoscopic resection, the StO₂ of each lesion was assessed using the oxygen saturation imaging. Five regions of interest were randomly selected from the lesion and surrounding mucosa. We calculated the average StO₂ measured at five sample points within each region of interest and then calculated the StO₂ difference between the lesion and surrounding mucosa. Furthermore, immunohistochemistry for hypoxia-inducible factor 1-alpha (HIF1α) was performed.</p> Results <p>In all groups, the mean StO₂ of the lesions was significantly lower than that of the surrounding mucosa (ADs, <i>P</i> &lt; 0.001; HPs, <i>P</i> = 0.005; SSLs, <i>P</i> &lt; 0.049). Lesions from patients with ADs revealed significantly greater StO₂ difference values between the lesion and surrounding mucosa than those from patients with HPs and SSLs (ADs vs. HPs, <i>P</i> &lt; 0.001; ADs vs. SSLs, <i>P</i> = 0.011), although there was no difference between the values for HPs and SSLs. Immunohistochemically, HIF1α expression was 39.7% in ADs, which was significantly higher than in HPs (0.0%, <i>P</i> &lt; 0.001) and SSLs (10.0%, <i>P</i> = 0.016). In ADs, there was a significant inverse correlation between StO₂ value and HIF1α expression (<i>P</i> &lt; 0.001).</p> Conclusions <p>StO₂ was significantly lower in ADs than in HPs, SSLs, and the surrounding mucosa, suggesting that ADs are more hypoxic than other polyps. Assessment of mucosal StO₂ using oxygen saturation imaging endoscopy might play an important role in distinguishing biologically aggressive colorectal neoplastic lesions.</p> Graphical abstract <p></p>