Background: Post-operative pain in laparoscopic cholecystectomy is variable, multifactorial and unpredictable.  The use of ultrasound-guided paravertebral nerve blocks (PVB) has been explored as part of its multi-modal pain management. Objective: To evaluate the efficacy of adding fentanyl and dexmedetomidine as adjuvants to bupivacaine in ultrasound guided paravertebral block for patients undergoing laparoscopic cholecystectomy. Patients and methods: This study was a prospective randomized controlled study that was conducted at Al-Azhar University Hospitals. The study included 90 patients who underwent US guided paravertebral block during laparoscopic cholecystectomy. The cases were randomly divided into three equal groups control bupivacaine group, the fentanyl group and the dexmedetomidine group. Results: visual analogue scale (VAS) during rest was statistically significantly lower in dexmedetomidine group at 1 hour, 2-hours, 6-hours, 12 hours and 24 hours postoperatively as compared with other groups. There were statistically significant differences found between the three groups regarding total dose of morphine. The total dose was statistically significantly lower in the dexmedetomidine group aa compared with the other groups. Conclusion: The use of a Dexmedetomidine as an adjuvant to bupivacaine was associated with less pain intensity and prolonged duration of analgesia as compared with fentanyl plus bupivacaine or bupivacaine alone, with no change or affection of the incidence of postoperative complications.