The hormone and neuropeptide oxytocin is believed to buffer against social stress and reduce social-threat perception. We employed a widely used ostracism paradigm, Cyberball, to investigate whether oxytocin ameliorated the acute behavioral and affective consequences of social rejection. In a double-blind, randomized, between-subjects design, 74 healthy male and female participants were administered intranasal oxytocin or placebo and subsequently ostracized or included during this virtual ball-tossing game. Ostracized participants reported negative affective and attachment-related reactions, as well as a significant motivational change in increased desire to be involved in the game; these effects were not influenced by oxytocin. Intranasal oxytocin did, however, increase included participants’ desire to play again with the same participants, suggesting oxytocin enhanced desire for future social engagement following inclusion. These findings are argued to provide evidence that the effects of oxytocin in promoting social approach behavior may be context specific and sensitive to positive social cues. The results suggest that in an explicitly aversive context, oxytocin does not buffer against the immediate impact of blunt social rejection.