Objective To evaluate the effect of esketamine combined with ropivacaine on rebound pain in patients with upper extremity fractures after brachial plexus block. Methods Patients who were admitted to Xuzhou Cancer Hospital from November 2021 to August 2022 and underwent open reduction and internal fixation for unilateral upper extremity fractures under brachial plexus block anesthesia were selected. According to the random number table method, they were divided into two groups: an esketamine group (RNK group, n=75) and a ropivacaine group (R group, n=74). Both groups were subjected to ultrasound‑guided supraclavicular brachial plexus block. The RNK group was administered with 0.375% ropivacaine and 0.5 mg/kg esketamine in 30 ml, while the R group was given 0.375% ropivacaine in 30 ml. Patient controlled intravenous analgesia (PCIA) with sufentanil was used in both groups after surgery. Then, their incidence of rebound pain within 48 h after brachial plexus block were recorded. Their mean arterial pressure (MAP) and heart rate were recorded upon entering the operating room, 5, 10, 20 min and 30 min after anesthesia, at skin incision, and at the end of surgery. Their onset times of sensory block and motor block, and the duration of sensory and motor block were recorded. The Numerical Rating Scale (NRS) scores at rest and during movement before surgery and at postoperative 8, 12, 24 h and 48 h were recorded. The consumption of sufentanil in PCIA pump at postoperative 24 h and 48 h, the total compression time and effective compression time were recorded. The incidence of other adverse reactions were recorded. Results Compared with the R group, the RNK group showed remarkable decreases in the incidence of rebound pain within 48 h after operation (P<0.05). Compared with those upon entering the operating room, the RNK group presented increases in MAP and heart rate 5 min and 10 min after anesthesia (P<0.05). Compared with those 5 min after anesthesia, the RNK group showed increases in MAP 10 min after anesthesia (P<0.05), and decreases in MAP and heart rate 20 min and 30 min after anesthesia, at skin incision and at the end of surgery (P<0.05). Compared with those 10 min after anesthesia, the RNK group presented decreases in MAP and heart rate 20 min and 30 min after anesthesia, at skin incision and at the end of surgery (P<0.05). Compared with the R group, the RNK group showed remarkable increases in MAP and heart rate 5 min and 10 min after anesthesia (P<0.05). The RNK group presented faster onset and longer duration of sensory and motor block than the R group (P<0.05). Compared with those upon entering the operating room, the R group presented decreases in NRS scores at rest and during movement at postoperative 8 h and 48 h (P<0.05), while the RNK group showed decreases in NRS scores at rest and during movement at postoperative 8, 12 h and 48 h (P<0.05). Compared with those at postoperative 8 h, the R group and RNK group presented increases in NRS scores at rest and during movement at postoperative 12, 24 h and 48 h (P<0.05). Compared with those at postoperative 12 h, the R group and RNK group showed increases in NRS scores at rest and during movement at postoperative 24 h (P<0.05), while the R group presented decreases in NRS scores at rest and during movement at postoperative 48 h (P<0.05). Compared with those at postoperative 24 h, the R group showed decreases in NRS scores at rest and during movement at postoperative 48 h, while the RNK group presented decreases in NRS scores during movement (P<0.05). Compared with the R group, the RNK group showed decreases in NRS scores at rest and during movement at postoperative 12 h and 24 h (P<0.05). There was no statistical difference in other indicators at other time points (P>0.05). Compared with the R group, the RNK group presented reduced consumption of sufentanil for PCIA at postoperative 12 h and 24 h, and reduced times of total and effective compression (P<0.05). There was no statistical difference in the incidence of other adverse reactions between the two groups (P>0.05). Conclusions Esketamine can be used as a ropivacaine adjuvant for ultrasound-guided supraclavicular brachial plexus block, which reduces the incidence of rebound pain after brachial plexus block, shortens the onset time and prolongs the duration of block.