Objectives To assess the effect of sound isolation versus music on the comfort of mechanically ventilated patients admitted to the intensive care unit (ICU) as a combined measurement of the hypnotic level, the level of sedation and the alteration of behaviour because of pain. Introduction Patients admitted to the ICU who require mechanical ventilation are surrounded by an ambient noise level ranging from 60 to 90 dB, well above the 40 dB recommended by the World Health Organization (WHO). Methods This was a randomized crossover clinical trial. Group A: sound isolation (1 h) followed by music (1 h); Group B: music (1 h) followed by sound isolation (1 h). Interventions were administered using noise‐cancelling headphones. The hypnotic level, the level of sedation and the alteration of behaviour because of pain was assessed using the bispectral index (BIS), the Ramsay scale and the behavioural pain scale (BPS), respectively. Statistical analysis of correlated data was performed using a generalized estimating equations (GEE) model. Results Of 130 patients assessed for eligibility, 82 were randomized to Groups A (n = 40) or B (n = 42). Mean age was 69 years (SD = 14), and 77·3% were men. A decrease of 4–5 points out of 100 during sound isolation and music therapy was recorded in BIS in both groups; the differences were not statistically significant compared with baseline scores. Likewise, no differences were observed in the scores obtained in the Ramsay scale and BPS. Conclusions Sound isolation and music intervention did not modify the comfort or physiological variables of mechanically ventilated critical patients from their respective baseline values. Relevance to clinical practice Music and sound isolation are potential strategies that could be used in nursing care to provide comfort to critical patients. Further studies should be undertaken to define the role of these new approaches and determine which groups of patients can benefit most from music or sound isolation.