Background: Along history, music has been used in a variety of ways for therapeutic purposes and has long been recognized for its physiological and psychological effects. Music listening can be an effective nursing intervention, to enhance relaxation, provide distraction, and reduce pain. Objectives: The aims of this study were to identify changes produced by different musical stimuli in blood pressure (BP), heart rate (HR), respiratory rate (RR), and oxygen saturations (SpO2) and to verify the influence of music listening on patients’ facial expressions with severe cerebral damage. Method: A quasiexperimental study was performed in 26 patients with severe cerebral damage, divided into control and case groups. Patients belonging to the case group were exposed to musical stimuli, radio, classical relaxing music (CRM), and relaxing music with nature sounds (RMNS). Patients were evaluated by measuring vital signs before and after exposure to each musical stimulus, as were the patients within the control group. Patients in the control group were exempt from any musical stimulus. Facial expressions were observed in each patient within the case group during the intervention. Results: The results show that radio produced a slight increase in systolic BP, HR, RR, and SpO2. The CRM induced a decrease of RR and an increase of SpO2 and also produced alterations of the facial expression. When RMNS was played, a decrease was displayed in BP, HR, and RR and an increase was displayed in SpO2. Alterations in facial expression were displayed in each patient. Conclusions: The results of the study suggest that the application of musical stimuli such as CRM and RMNS can be used to provide a state of relaxation in patients with severe cerebral damage.