Withdrawal from opioids is associated with a highly aversive affective state, and avoidance of this state is a main reason people with opioid use disorder continue to use or relapse to opioids. Activity in the ventral pallidum (VP) is necessary for opioid relapse after withdrawal. Recent studies from our group and others have shown that glutamatergic VP neurons (VPGlu) constitute a unique subpopulation of VP neurons, and that VPGlu activity constrains reward seeking, particularly in decision-making tasks where negative consequences are associated with choosing a reward. However, how self-administration and withdrawal from prescription opioids alters the function of VPGlu neurons and their activity in conflicted decision-making tasks is completely unknown. With fluorescent in situ hybridization, we discovered that VPGlu neurons are enriched in mu opioid receptors. Patch-clamp electrophysiology experiments revealed that application of mu opioid agonists decreased excitability of VPGlu. Thus, we predicted that self-administration of oxycodone, the mu opioid receptor agonist, would potently modulate function of these neurons. Indeed, protracted abstinence from oxycodone increased the intrinsic excitability of VPGlu neurons and their synaptic output. Using in vivo calcium imaging we investigated the basal activity of VPGlu neurons throughout oxycodone self-administration to determine whether the response of these neurons is altered throughout opioid exposure. Given our previous work showing that activation of VPGlu neurons is highly aversive, we hypothesize that these opioid-induced adaptations contribute to the aversive state of drug withdrawal that drives opioid relapse through negative reinforcement.