Sleeve gastrectomy has become a popular and effective treatment for morbidly obese patients. The aim of this prospective randomized study was to assess the efficacy of multimodal analgesia using pregabalin and dexmedetomidine in morbidly obese patients undergoing laparoscopic sleeve gastrectomy. After ethical approval 60 American Society of Anesthesiologists (ASA) physical status II patients were enrolled in this study and allocated randomly into 2 groups: group A received 75mg oral pregabalin 2h before surgery and dexmedetomidine infusion 0.4μg/kg/h and group B (control group) received placebo capsule 2h before surgery and saline infusion intraoperatively. Intraoperative fentanyl consumption, hemodynamics and postoperative opioid consumption, pain scores, level of sedation and any side effects were evaluated. There was a significant decrease in heart rate, mean arterial blood pressure, pain score, intraoperative fentanyl use, postoperative morphine consumption and nausea verbal rating scale in group A compared to group B. There was a significant increase in sedation score in group A compared to group B. The combination of preoperative oral pregabalin and intraoperative dexmedetomidine infusion decreased intraoperative fentanyl use and ensured postoperative better pain control and less postoperative opioid consumption.