This study examined the predictive power of spiritual wellness on depression in 83 mothers of children with autism spectrum disorders. Spiritual wellness is a multidimensional construct that consists of four components: meaning and purpose in life, inner resources, transcendence, and positive interconnectedness. Each of the four spiritual components of spiritual wellness was investigated to determine their respective predictive power in predicting lower depression symptoms. Spiritual wellness components that were found to be significant predictors of lower depression symptoms in mothers were identified as protective factors. A hierarchical regression revealed that the spiritual wellness components of meaning and purpose in life and inner resources were significant predictors of lower depression symptoms and therefore served as protective factors in maternal depression. The findings of this study provide direction for future research to investigate how these spiritual wellness components can be incorporated into counseling and the design of interventions for mothers of children with autism spectrum disorders.