Oxytocin is known to promote social affiliation. The mechanism by which this occurs is unknown, but it may involve changes in social information processing. In a placebo-controlled study, we examined the influence of intranasal oxytocin on effortful and automatic attentional shifting in 57 participants using a spatial cueing task with emotional and neutral faces. For effortful processing, oxytocin decreased the speed of shifting attention to sad faces presented for 750 ms and facilitated disengagement from right hemifield sad and angry faces presented for 200 ms. For automatic processing, symptoms of depression moderated the relationship between drug and disengagement. Oxytocin attenuated an attentional bias to masked angry faces on disengagement trials in persons with high depression scores. Oxytocin's influence on social behavior may occur, in part, by eliciting flexible attentional shifting in the early stages of information processing.