The personal experience of pain is complex and depends on physiological and psychological factors. From this latter category, pain catastrophizing plays an important role in pain behavior and response. We aimed to determine the effect of pain catastrophizing on central nociceptive processing in healthy individuals. Functional MRI was performed during two pain intensity levels evoked by electrical median nerve stimulation in 22 healthy individuals. Pain catastrophizing scores were determined for all subjects. Pain catastrophizing was not related to activity in regions associated with sensory-discriminative aspects of pain, such as the primary or secondary somatosensory cortex. Instead, during mild pain, there was a relationship between catastrophizing and activity in cortical regions associated with affective, attention, and motor aspects of pain, including dorsolateral prefrontal, insula, rostral anterior cingulate, premotor, and parietal cortices. During more intense pain, prefrontal cortical regions implicated in the top-down modulation of pain were negatively correlated with catastrophizing. These findings can be viewed from the framework of an attention model of pain catastrophizing, whereby a cortical vigilance network is engaged during mild pain, but diminished prefrontal cortical modulation impedes disengaging from and suppressing pain during more intense pain. These findings may also implicate catastrophizing in the progression to or persistence of chronic pain.