Background: Since the introduction of Erector Spinae Plane Block (ESPB) in 2016 it has been used with success in various thoracic, abdominal, and back surgeries. Many theories have been suggested for its mechanism of action, although the exact mechanism remains unknown. Spine surgeries result in significant postoperative pain, while using postoperative opioids provide adequate pain control in most of the cases, some cases still suffer from uncontrolled pain and patients receiving multiple doses of opioids suffer from various side effects including postoperative nausea and vomiting, constipation, and delayed ambulation. The aim of the study was to compare between the adjuvant effect of dexmedetomidine and magnesium sulfate given along with bupivacaine 0.25% in ESPB. Methods: This was a prospective randomized single blinded study including 52 patients divided in 2 groups; one receiving ESPB with a combination of bupivacaine 0.25% and magnesium sulfate and the other receiving the same block with a combination of bupivacaine 0.25% and dexmedetomidine. Statistical analysis for data collected was done using the (Statistical Package for the Social Sciences) version 26. Shapiro-Wilk test was used to check the normality of the data distribution. Quantitative variables were expressed as mean and standard deviation, median, inter-quartile range, minimum and maximum as appropriate. Results: The group receiving bupivacaine and dexmedetomidine showed a significant decrease in intraoperative pulse and blood pressure compared to the other group (p< 0.05). They showed a prolonged postoperative analgesia duration as well and a decreased total opioid consumption (p< 0.05). Conclusion: Although dexmedetomidine results in prolonged postoperative analgesia duration compared to magnesium sulfate when combined with bupivacaine 0.25% in ESPB, its negative effects on hemodynamics should be considered. Trial registration: This trial was registered retrospectively on Clinicaltrials.gov registry (NCT05694897) on 23/1/2023.