The aim of this study was to investigate the effectiveness of music therapy on the severity of pain, perceived stress and happiness in adolescents with leukemia in Ahvaz city. This quasiexperimental study was carried out with a pretest, post-test, and follow-up with the control group. The statistical population included all adolescents with leukemia in Ahvaz city. A total of 30 adolescents with leukemia were selected using available sampling method and assigned randomly into two groups of experimental and control. McGill pain intensity questionnaire, Perceived Stress Scale and Oxford Happiness Inventory were used to collect data. After forming the groups (experimental and control) and performing the pre-test on both groups, the experimental group received 12 sessions of music therapy and the control group did not receive intervention. After the end of the intervention, they were tesed again in post test, and 30 day afterward in follow phases. Analysis of the data using multivariate and one-way covariance analysis showed that music therapy was effective in reducing the severity of perceived pain, and increased happiness in adolescents with leukemia. However, these results were not found to be significant in the follow up phase; hence, music therapy had no sustained effect in reducing the intensity of pain and perceived stress; also it did not increase the happiness of adolescents with leukemia. According to these results, music therapy can be used as a therapeutic approach to reduce the intensity of pain and perceived stress, as well as to increase the happiness of adolescents with leukemia.