Abstract: Objective To explore the effects of propofol sedation on psychological stress in patients undergoing surgery under epidural anesthesia. Methods Sixty patients scheduled to undergo elective ileostomy closure under epidural anesthesia were randomized into propofol sedation group and control group (n=30). The patients in the sedation group received a loading dose of propofol of 0.6 mg·kg- 1 · h- 1 followed by a maintenance dose with continuous infusion of 3 mg·kg- 1 · h- 1 given after the Observer’s Assessment of Alertness/Sedation (OAA/S) score reached 2-3. An equivalent volume of normal saline was administered in patients in the control group. The patients’ preoperative and intraoperative anxiety scores were assessed with the State Anxiety Inventory (SAI) on the day before and on the first day after the surgery, respectively. The mean blood pressure (MBP), heart rate (HR), SpO2, OAA/S, and the indicators of psychological stress of brain functional state of the patients (including the wavelet index [WLi], anxiety index [ANXi], comfortable index [CFi] and pain index [Pi]) were recorded at 5 min after entering the operating room (T0), at the time of lumbar puncture (T1) and change to supine position after the puncture (T2), at 20 s (T3), 40 s (T4), and 60 s (T5) after intravenous administration, and at 2 min (T6), 4 min (T7), 6 min (T8), 8 min (T9), 10 min (T10) and 40 min (T11) after skin incision. The patient’s satisfaction with anesthesia was assessed with the Visual Analog Scale (VAS) score on the first day after the operation. Serum cortisol level was measured before anesthesia and at the end of operation to calculate the changes in cortisol level. Results The two groups of patients were comparable for preoperative SAI scores (P>0.05); The patients in the sedation group appeared to have lower intraoprative SAI scores, but this difference was not statistically significant (P=0.05). MBP, HR, and SpO2 at the time points from T6 to T10 and OAA/S, WLi, ANXi, CFi, and Pi at the time points from T6 to T11 were significantly lower in the sedation group (all P<0.05), and these parameters were not significantly different between the two groups at the other time points (all P>0.05). The patient satisfaction scores were significantly higher in the sedation group (Z=2.07, P<0.05). Compared with the preoperative levels, serum cortisol level at the end of the operation was increased in the sedation group but lowered in the control group, and the variations of serum cortisol level differed significantly between the two groups (t=4.75, P<0.01). Conclusion Intraoperative propofol sedation can alleviate the patients’ anxiety, improve the comfort level, and lessen physiological stress during surgeries under epidural anesthesia.