The study aimed to identify the nature of the relationship between self- compassion and depression among mothers with intellectual disability. It also aimed to identify the nature of the relationship between psychological well-being and depression among mothers with intellectual disability. As well as to identify the impact of the interaction of both self- compassion and psychological well-being to reduce depression among mothers with intellectual disability. Finally analyzing the pathways of the relationship between self-compassion, psychological well-being and depression among mothers with intellectual disability. The study sample was 261 mothers of children with mental disabilities who were selected from Fayoum and Qalioubia governorates. Tools were the self-compassion scale prepared by Abdulrahman and his colleagues (2015), the psychological well-being scale prepared by the researchers, and the Beck Depression List. Methodology was descriptive - comparative causal study. Results indicated that there is a negative correlation between negative self-compassion and depression. It also indicated a negative correlation between psychological well-being and depression, as well as the effect of the interaction of self-compassion and psychological well-being on the feeling of depression in the study sample. The model of the path analysis of the relationship between self-compassion, psychological well-being and depression achieved good conformity