Introduction: Brachystegia eurycoma (Fabaceae) has been reported to mitigate peripheral and centrally mediated nociception. However, the probable mechanisms involved in this antinociceptive effect have not been investigated. This study evaluated the possible mechanisms involved in the antinociceptive effect of Brachystegia eurycoma (BE). Methods: Mice were selected according to standard protocols. They were treated with 100, 200 and 400 mg/kg, per oral of BE. One (1) hour post-treatment, 0.6 %v/v acetic acid (10 ml/kg, ip) was administered, and the number of writhes was recorded every 5 mins for 30 mins. To investigate the possible mechanisms involved in the antinociceptive effect of BE, mice (n = 5) were pretreated with atropine (1.0 mg/kg, ip), naloxone (1.0 mg/kg, ip), haloperidol (0.1 mg/kg, ip), and ondansetron (1.0 mg/kg, ip), followed by treatment with BE (100 mg/kg, po) after 15 mins. 1-hour post-treatments, 0.6 %v/v acetic acid (10 ml/kg, ip) was administered, and the number of writhes was recorded for 30 mins. In vitro radical activity, total phenol and flavonoid contents were also determined. Results: BE reduced writhing at all doses, exerting peak reduction at 100 mg/kg compared to control (130.3 ± 3.1 vs 64.8 ± 3.5, p < 0.05). Naloxone caused a 24 % reversal in the antinociceptive effect of BE (p < 0.05). BE exerted a concentration-dependent radical scavenging activity with an IC50 (2.4 µg/kg) higher than ascorbic acid. The total phenol content of the BE extract was estimated to be 156.1 ± 1.4 µg/ml GAE/g extract, while the total flavonoid content was determined to be -11.9 ± 3.2 mg QE/g extract. Conclusion: The antinociceptive effect of BE partly involves the stimulation of opioid receptors and reduction in radical-induced nociception. However, further investigation would be needed to elucidate the mechanism involved with its antinociceptive activity. Keywords: Brachystegia eurycoma, antinociceptive, acetic acid, opioid, radical scavenging