BACKGROUND: The default mode network consists of a set of functionally connected brain regions (posterior cingulate, medial prefrontal cortex and bilateral parietal cortex) maximally active in functional imaging studies under "no task" conditions. It has been argued that the posterior cingulate is important in consciousness/awareness, but previous investigations of resting interactions between the posterior cingulate cortex and other brain regions during sedation and anesthesia have produced inconsistent results. METHODOLOGY/PRINCIPAL FINDINGS: We examined the connectivity of the posterior cingulate at different levels of consciousness. "No task" fMRI (BOLD) data were collected from healthy volunteers while awake and at low and moderate levels of sedation, induced by the anesthetic agent propofol. Our data show that connectivity of the posterior cingulate changes during sedation to include areas that are not traditionally considered to be part of the default mode network, such as the motor/somatosensory cortices, the anterior thalamic nuclei, and the reticular activating system. CONCLUSIONS/SIGNIFICANCE: This neuroanatomical signature resembles that of non-REM sleep, and may be evidence for a system that reduces its discriminable states and switches into more stereotypic patterns of firing under sedation.