This study is aimed at investigating aspects of personality effects and perceived social support on marital instability regarding the mediating role of occupational stress among married female nurses in Shiraz hospitals. Utilizing Cochran’s formula as sample population and random sampling method for selection, among female nurses with at least three years of marriage (2245 nurses), 246 nurses was calculated. According to this method, all sample nurses had equal chance to be selected. Data collection was carried out usingfour standard questionnaires of NEO personality inventory (Costa & McCrae, 1986), the multidimensional scale of perceived social support (Zimet et al, 1988), nurse job stress inventory (Gray-Toft & Anderson, 1981) and marital instability questionnaire (Booth et al., 1983). The descriptive analysis was done by SPSS 16 and LISREL structural equations were used to validate the model. The results showed that majority of subjects have a consistent and conscientious character, high social support and moderate occupational stress. They had the lowest marital instability with 22% possibility of divorce. The correlation test results showed that neuroticism has a positive relationship and other aspects of personality have a negative relationship with the marriages instability. The perceived social support has a negative relationship and the occupational stress has a positive relationship with marital instability. Structural equation modeling results showed that the conceptual model had a good fitting. Therefore, the aspects of personality and perceived social support had a direct and indirect impact on marital instability. Finally, the personality aspects were determined as the most important prediction variable of marital instability in nurses.