Attention impairments are common symptoms of posttraumatic stress disorder (PTSD); however, the nature of these impairments remains elusive. Attention impairment may arise as the result of either excessive response to task-irrelevant stimuli or reduced response to task-relevant information. To test the association between PTSD and response to task-relevant and task-irrelevant stimuli, we used a 3-tone novelty auditory oddball task (AOD). We hypothesized that participants with PTSD relative to trauma controls would have less response during novelty processing in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex, as well as less response in the dlPFC and the orbitofrontal cortex during target detection. Thirty-one male veterans completed a 3-tone novelty AOD task during functional magnetic resonance imaging. Compared to trauma controls, the PTSD group had reduced response during novelty processing in ventromedial prefrontal cortex, superior/middle frontal gyrus (dlPFC), supplementary motor area/caudate, and in posterior regions including bilateral posterior cingulate cortex. The current results suggest PTSD is associated with a pattern of reduced response to novel stimuli. A disturbed orienting response in these brain regions could theoretically underlie PTSD attention-related symptoms.