Background: The use of opioids in surgeries for morbidly obese patients could cause respiratory depression. Therefore, alternative analgesics are needed to improve anesthetic management for obese patients. The objective of this study was to compare the effect of dexmedetomidine and clonidine on pain as well as analgesic consumption at 24 h postoperatively in patients undergoing laparoscopic gastric sleeve. The secondary objective was to compare patients′ and surgeons′ satisfaction. Materials and Methods: A total of 60 obese and morbidly obese patients scheduled to undergo laparoscopic gastric sleeve were randomly assigned into two groups. 10 min after induction of general anesthesia, one group received 0.8-1.2 μg/kg/30 min intravenous (IV) clonidine through 500 mL lactated Ringer′s solution and placebo (normal saline solution) through syringe pump. The second group received IV dexmedetomidine through syringe pump at a rate 0.5-0.8 μg/kg/h and placebo through 500 mL lactated Ringer′s solution. Data on pain, analgesic consumption, and return to normal activity in addition to patients′ and surgeons′ satisfaction were collected. Results: Both groups were similar with respect to demographic and intraoperative hemodynamic characteristics. Fentanyl consumption, surgery duration and hospital stay were similar for the two groups. Pain scores on walking were significantly lower in the clonidine group at 12 h postoperatively (P = 0.014) compared with dexmedetomidine group. The number of patients who consumed pethidine was significantly lower in the clonidine group at 12 h postoperatively (P = 0.045). Conclusion: This study concluded that clonidine and dexmedetomidine yielded similar outcomes with a difference in pain and analgesic consumption at 12 h postoperatively.