ABSTRACT Introduction People admitted to the intensive care unit (ICU) who require mechanical ventilation (MV) must complete the weaning process as soon as possible to reduce associated risk factors. Previous research suggests that music therapy may be beneficial for improving breathing capacity and relaxation, but studies related to weaning are limited. This article presents a music therapy protocol for a randomised controlled trial (RCT). Method ICU patients aged 18–80 who meet the clinical criteria for initiating weaning are eligible for this RCT with two parallel groups. Participants (n = 100) are randomly assigned to a control group (receiving standard treatment during weaning) and an intervention group (receiving daily music therapy intervention combined with standard treatment). The outcome measures are (1) duration of weaning in hours, (2) dosage of sedatives and analgesia, (3) agitation, (4) delirium, (5) perception of pain, and (6) perceived stress at 90 days follow-up. During music therapy, (7) blood pressure, heart rate, respiratory rate and oxygenation level are only measured in the intervention group. The flexible music therapy protocol addresses patient needs from a humanistic biopsychosocial perspective. It includes an assessment of individual music preferences (adapted from the Musical Life Story Questionnaire) and methods such as entrainment, clinical instrumental improvisation, songwriting, and receptive music therapy to reinforce breathing capacity and promote relaxation, stimulation, communication, and emotional regulation. Discussion The findings of this study may offer relevant implications for healthcare delivery and the application of music therapy during weaning in the ICU.