Objective The present investigation sought to examine the simultaneous effects of anxiety sensitivity and pain-related anxiety on fear and anxious responding to a 10% carbon dioxide enriched air challenge. Methods Participants included 247 adults (53% women; mean age=21.91 years, S.D.=8.41) recruited from the community. At the laboratory, participants were administered a structured clinical interview, completed a battery of self-report measures, and underwent a 10% carbon dioxide enriched air challenge. Results Both anxiety sensitivity and pain-related anxiety were significantly and uniquely predictive of post-challenge panic attacks, total post-challenge panic attack symptoms, and intensity of cognitive panic attack symptoms. Anxiety sensitivity, but not pain-related anxiety, also was predictive of post-challenge physical panic symptoms. The observed significant effects for both anxiety sensitivity and pain-related anxiety were evident above and beyond the variance accounted for by gender, age, current level of nonspecific bodily pain, and negative affectivity. Neither anxiety sensitivity nor pain-related anxiety was significantly predictive of change in anxiety focused on bodily sensations or heart rate. Conclusion Results suggest that anxiety sensitivity and pain-related anxiety, although related to one another, may be independently important variables underlying fear reactivity to bodily sensations.