Background <p>Ketamine, an intravenous anesthetic with antidepressant properties, may influence sleep quality through glutamatergic and circadian modulation. This study aimed to evaluate the effect of low-dose ketamine on Pittsburgh Sleep Quality Index (PSQI) on the 7th day following administration, using colonoscopy as a standardized procedural model.</p> Methods <p>This randomized, controlled, double-blind trial included 249 patients assessed for eligibility, of whom 71 were excluded. 178 patients undergoing colonoscopy between July 30 and October 6, 2024, were allocated into two groups: the ketamine group (n = 89), receiving propofol with low-dose ketamine, and the control group (n = 89), receiving only propofol. After follow-up, 164 patients (82 per group) were included in the final analysis. The primary outcome of this study was the PSQI score on post-procedure day 7. The secondary outcomes included the Sleep Numeric Rating Scale (NRS-s) and the Richards-Campbell Sleep Questionnaire (RCSQ) scores on post-procedure day 7, as well as anesthesia-related complications analysed as a composite outcome (components also examined individually), and patient satisfaction with anesthesia.</p> Results <p>Postoperative PSQI scores were significantly lower in the ketamine group (p = 0.005), while NRS-s and RCSQ scores showed no significant difference (p = 0.617, p = 0.072). The change in PSQI scores was greater in the ketamine group (p = 0.025). Composite anesthesia-related complications were lower with ketamine (p = 0.022); in component-wise analyses, procedure-disrupting movements were also less frequent (p = 0.021). However, higher rates of restless dreams and hallucinations were observed, and patient satisfaction was higher (p &lt; 0.001, p &lt; 0.001, and p = 0.002, respectively).</p> Conclusions <p>Low-dose ketamine was associated with improved postoperative PSQI scores, suggesting a potential short-term benefit on sleep quality in patients without sleep disorders. However, the lack of consistent improvement across other sleep measures warrants cautious interpretation and further investigation. Additionally, ketamine reduced composite anesthesia-related complications but increased psychomimetic effects.</p> Clinical Trials <p><a href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</a>; Registration Number: NCT06498869; Registration Date: July 6, 2024.</p>