This study examined the reliability and validity of the Patient Reported Outcomes Measurement System (PROMIS)-25, a profile instrument consisting of four-item fixed short forms for six health domains, in children living with burn injury. Data were provided by children participating in a multi-center longitudinal study of outcomes after burn injury. Floor and ceiling effects, unidimensionality, internal consistency, reliability, and differential item functioning (DIF) of the PROMIS-25 Profile v.2.0 were examined. Correlations with other established measures were calculated to assess concurrent validity. Children (n = 256) between the ages of 8-18 years with moderate to severe injury provided responses on PROMIS-25 domains. All PROMIS-25 domains showed high internal consistency. Substantial portions of the sample reported no symptoms (anxiety [58.2%], depressive symptoms [54.6%], fatigue [50.8%], pain [60.1%]). There was a large ceiling effect on peer relationships (46.8%) and physical function mobility (57.5%). One-factor confirmatory factor analyses supported unidimensionality for all domains. Reliability was sufficient for group mean comparisons (>0.8) across at least some trait levels for most domains except fatigue and anxiety. No DIF with respect to burn status was detected when comparing the burn sample to the PROMIS pediatric general U.S. population testing sample. These results provide evidence of reliability and validity of PROMIS-25 scores among children living with burn injury. Reliability of domains was low to moderate and would likely be improved, and ceiling effects reduced for some domains, by administering the PROMIS-37, which includes six items per domain.