The present study compared neural activity in participants with blunted (N = 9) or exaggerated (N = 8) cardiac stress reactions. Neural activity was recorded with fMRI while participants performed a validated stress task and control task. Exaggerated reactors exhibited significant increases in heart rate from control to stress task, whereas blunted reactors had no change in heart rate. Blunted reactors also had reduced activation in the anterior midcingulate cortex and insula compared to exaggerated reactors during the stress condition, and a greater deactivation in the amygdala and posterior cingulate. The biological differences between groups in response to the stress task could not be explained by subjective measures of engagement, stressfulness, or difficulty. This study supports the notion that blunted peripheral physiological stress reactivity may be a marker of a corresponding under-recruitment of brain systems during behavioral states requiring motivated action.