• Background Music is considered an ideal therapy for reducing stress in patients receiving mechanical ventilation. Previous studies of the effect of music on stress in such patients have focused solely on indirect markers of the stress response rather than on serum biomarkers. • Objective To explore the influence of music on serum biomarkers of the stress response in patients receiving ventilatory support. • Methods A convenience sample of 10 patients receiving mechanical ventilation was recruited from an 11-bed medical intensive care unit. Patients were randomly assigned to listen to music or to rest quietly for 60 minutes. Levels of corticotropin, cortisol, epinephrine, and norepinephrine were measured 4 times during the 60 minutes. • Results The levels of the 4 biomarkers of the stress response did not differ significantly between patients who listened to music and patients who rested quietly, though the levels of corticotropin and cortisol showed interesting trends. • Conclusions Additional research is needed with a larger sample size to evaluate further the influence of music on biochemical markers of the stress response in patients receiving mechanical ventilatory support. In future studies, confounding factors such as endotracheal suctioning and administration of medications that influence the stress response should be controlled for.