Background: Infertility is a multi-aspect problem; it can cause major disturbances with emotional, social and psychological consequences including loss of life satisfaction. Spirituality is considered as an important source for individuals to adapt with stressful life events. Objectives: The current study aimed to determine the relationship between spiritual well-being and life satisfaction in females with infertility. Methods: After explaining the study goals to the subjects and attaining their written consents, the present cross-sectional corelational study was conducted on 190 females with infertility referred to Isfahan fertility and infertility center, Isfahan, Iran. The subjects were selected through a convenience random sampling method in three months by the satisfaction with life scale (SWLS) and spiritual well-being scale (SWBS) through face to face interview in 2013. Data were collected and then analyzed by SPSS ver. 17. Descriptive statistical methods (frequency distribution, mean, variance and standard deviation tables) and analytical statistical methods (Pearson correlation test, Spearman correlation coefficients, one-way ANOVA and T-test) were used. Results:The results of the study indicated a direct relationship between the scores of life satisfaction and religious dimension of spiritual well-being (r = 0.375, P < 0.001), as well as the score of existential dimension of spiritual well-being (r = 0.732, P < 0.001), and the overall score of spiritual well-being (r = 0.643, P < 0.001). The score of existential dimension had a closer relationship with that of life satisfaction, compared to the score of religious dimension and the overall score of spiritual well-being. Conclusions: The present study showed that people with higher spiritual well-being had a higher life satisfaction. Since infertility has numerous social and psychological complications and consequences, which can lead to lower life satisfaction, the medical staff can increase spiritual well-being and life satisfaction in females with infertility problems by taking proper measures and actions.