The aim of this research was to investigate the relationship between marital satisfaction, depression and immune system in spouses of Ahvaz. The sample consisted of 30 couples who were selected randomly from 52 couples and they were matched from age, educational status, physical and mental disorders and other criteria considered in this research. The instruments were Hudson marital satisfaction inventory and Beck major depression inventory (BDI).Also their immune system was assessed through blood sample. The results revealed that there was a significant positive relationship between marital satisfaction and CD4, CD4/CD8, and NK cells (CD16, CD56). Also, there was a significant negative relationship between marital satisfaction and depression. In addition, there was a significant difference between male and female in immune system and depression. The rate of depression in female was higher than male, but the rate of immune system in male was higher than female. Further, the results of this research indicated that marital satisfaction and depression explained %17 of most role to predict the immune system. Also, the role of marital satisfaction was more than depression to predict the immune system.