The purpose of this study was to test the measurement invariance of the Brief Symptom Inventory's (BSI) secondary factor model across African, white, and Latino Americans using multiple-group confirmatory factor analyses. This study provides an examination of the BSI's validity for use in mental health service research for people with severe and persistent mental illness (SPMI). The sample consisted of 1,166 individuals receiving treatment for SPMI in a publicly funded mental health system in Los Angeles, California. The results showed that the secondary factor model fit the data very well. The findings suggest that the BSI can be used with African, white, and Latino Americans diagnosed with SPMI to assess their psychological distress and that it can be useful in comparing systematic group differences in observed means and covariance matrices across the three ethnic groups. It is recommended that the nine subscale scores and the Global Severity Index score of the BSI be used in practice and research with African, white, and Latino Americans with SPMI.