In the past two decades several attempts have been made to promote a correct diagnosis and possible restorative interventions in patients suffering from Disorders of Consciousness (DOC). Sensory stimulation has been proved to be useful in sustaining the level of arousal/awareness and to improve behavioral responsiveness with a significant effect on oro-motor functions. Recently, action observation has been proposed as a stimulation strategy in DOC patients, based on neurophysiological evidence that the motor cortex can be activated not only during action execution, but also when actions are merely observed in the absence of motor output, or during listening to action sounds and speech. This mechanism is provided by the activity of mirror neurons. In the present study, a group of patients with DOC (11 males, 4 females; median age: 55 years; age range 19-74 years) underwent task-based functional MRI in which they had, in one condition, to observe and listen to the sound of mouth actions, in another condition, to listen to verbs with motor or abstract content. In order to verify the presence of residual activation of the mirror neuron system, brain activations of patients were compared with that of a group of healthy individuals (7 males, 8 females; median age: 33.4 years; age range: 24-65 years) preforming the same tasks. The results show that brain activations were lower in DOC patients compared with controls, except for primary auditory areas. During the audiovisual task, 5 out of 15 DOC patients showed only residual activation of low-level visual and auditory areas. Activation of high-level parieto-premotor areas was present in 6 patients. During the listening task, 3 patients showed only low-level activations, and 6 patients activated also high-level areas. Interestingly, in both tasks, one patient with a clinical diagnosis of vegetative state showed activations of high-level areas. Region of interest analysis on Blood Oxygen Level Dependent (BOLD) signal change in temporal, parietal and premotor cortex revealed a significant linear relation with the level of clinical functioning, assessed with Coma Recovery Scale-Revised. We propose a classification of the patient’s response based on the presence of low-level and high-level activations, combined with patient’s functional level. These findings support the use of action observation and listening as possible stimulation strategies in DOC patients and highlight the relevance of combined methods based on functional assessment and brain imaging to provide more detailed neuroanatomical specificity about residual activated areas at both cortical and subcortical levels.