OBJECTIVES: This study examined whether the administration of intranasal oxytocin was associated with pain sensitivity, endogenous pain inhibitory capacity, and negative mood states. MATERIALS AND METHODS: A total of 30 pain-free, young adults each completed 3 laboratory sessions on consecutive days. The first session (baseline) assessed ischemic pain sensitivity, endogenous pain inhibition via conditioned pain modulation (CPM), and negative mood using the Profile of Mood States. CPM was tested on the dominant forearm and ipsilateral masseter muscle using algometry (test stimulus) and the cold pressor task (conditioning stimulus; nondominant hand). For the second and third sessions, participants initially completed the State-Trait Anxiety Inventory and then self-administered a single (40 IU/1 mL) dose of intranasal oxytocin or placebo in a randomized counterbalanced order. Thirty minutes postadministration, participants again completed the State-Trait Anxiety Inventory and repeated assessments of ischemic pain sensitivity and CPM followed by the Profile of Mood States. RESULTS: Findings demonstrated that ischemic pain sensitivity did not significantly differ across the 3 study sessions. CPM at the masseter, but not the forearm, was significantly greater following administration of oxytocin compared to placebo. Negative mood was also significantly lower following administration of oxytocin compared to placebo. Similarly, anxiety significantly decreased following administration of oxytocin but not placebo. DISCUSSION: This study incorporated a placebo-controlled, double-blind, within-subjects crossover design with randomized administration of intranasal oxytocin and placebo. The data suggest that the administration of intranasal oxytocin may augment endogenous pain inhibitory capacity and reduce negative mood states including anxiety.