Background Acute post-operative pain is a predictor in the development of chronic pain after laparoscopic cholecystectomy. Music has been shown to reduce surgical stress. In a randomized, clinical trial, we wanted to test the hypothesis that perioperative and post-operative soft music reduces pain, nausea, fatigue and surgical stress in patients undergoing laparoscopic cholecystectomy as day surgery. Method The study was performed in otherwise healthy Danish patients eligible for day surgery. Ninety-three patients were included and randomized to either soft music or no music perioperatively and post-operatively. Using visual analog score pain, nausea and fatigue at baseline, 1 h, 3 h, 1 day and 7 days after surgery were recorded. C-reactive protein and cortisol were sampled before and after surgery. Results Music did not lower pain 3 h after surgery, which was the main outcome. The music group had less pain day 7 (P = 0.014). Nausea was low in both groups and was not affected by music. The music group experienced less fatigue at day 1 (P = 0.042) and day 7 (P = 0.015). Cortisol levels decreased during surgery in the music group (428.5-348.0 nmol/l), while it increased in the non-music group (443.5-512.0 nmol/l); still, the difference between the two groups were only significant using general linear models as post-hoc analysis. Soft music did not affect C-reactive protein levels. Conclusion Soft music did not reduce pain 3 h after laparoscopic cholecystectomy. Soft music may reduce later post-operative pain and fatigue by decreasing the surgical stress response.