Cannabidiol, a major non-psychoactive constituent of cannabis, has generated interest as a novel therapeutic for managing several pathological conditions including chronic pain and opioid use disorder. Here, we evaluated the effects of cannabidiol (3.2 or 10.0 mg kg-1) on the antinociceptive and the reward-related effects of the opioid analgesic oxycodone (0.56 mg kg-1) in rats using an operant pain assay, locomotor activity monitoring, and the conditioned place preference paradigm. We also assessed pharmacokinetic and pharmacodynamic interactions between cannabidiol and oxycodone in plasma and brain. Cannabidiol enhanced the antinociceptive effect of oxycodone without affecting oxycodone-induced behavioral sensitization, or the acquisition and expression of oxycodone conditioned place preference. Cannabidiol coadministration with oxycodone reduced levels of the oxycodone metabolite noroxycodone in the plasma and increased levels of oxycodone in the brain, while oxycodone coadministration increased levels of the cannabidiol metabolite 7-carboxycannabidiol in plasma. Rats that received oxycodone generally showed higher levels of biogenic amines across the brain, whereas those administered cannabidiol alone or oxycodone plus cannabidiol showed similarly lower levels. This indicates coadministration of cannabidiol has central neurochemical actions distinct from administration of oxycodone alone. Together, these findings suggest that cannabidiol potentiates the analgesic effects of oxycodone without affecting its reward-related properties, and this dichotomy appears to be due to complex pharmacological interactions between cannabidiol and oxycodone in the brain. As such, cannabidiol may hold promise as an opioid sparing approach to managing pain.