Indonesia is listed at number 7 out of 10 countries with the highest infant mortality in the word based on WHO 2019 data. The most commond cause of infant mortality in Indonesia is low birth weight which can occur in premature babies. Vital sign are body parameters to assess the physiological function of the body’s vital organs or the body’s homeostatic mechanism. Various problems in premature infants include the risk of infection, difficulty breathing, hypothermia, poor sucking reflex, nutritional disorder, hypoglycemia, intracranial bleeding, meconium aspiration syndrome and hyperbilirubinemia. Premature babies are at risk for respiratory problems and impaired growth and development due to organ immaturity. Some interventions that can improve the health condition and growth and development of premature babies are massage therapy and music therapy. This study aims to determine the effectiveness of the combination of infant massage therapy and music on respiratory frequency and body weight in premature infants. The research method is quantitative using a quasi experiment with one group pre and posttest without control design on 10 premature babies, giving a combination of massage and music therapy for 7 days. The result of the Paired-sample t-Test showed p value 0,000 < 0,05 in respiratory frequency and p value 0,047 < 0,05 in body weight. These result indicate that the combination of massage therapy and music is effective on respiratory frequency and weight of premature babies.