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Objectives: The aim of this study was to estimate the effect of changes in depressive symptoms on health-related quality of life (HRQoL) in couples. This was examined before, during and after the pregnancy. In addition, (HRQoL) was examined in relation to the mode of delivery., Methods: A prospective longitudinal study of 416 couples was conducted in two teaching hospitals in Tehran, Iran. The translated Medical Outcomes Study-Short Form 36 (SF-36) and the Edinburgh Postnatal Depression Scale (EPDS) were used to measure health-related quality of life and depressive symptoms respectively, and are reported here., Results: The results showed that women and their spouses experienced a noticeable decline in their physical HRQoL during and after the pregnancy. However, their mental health functioning showed a significant improvement following conception. The prevalence of depressive symptoms was high but decreased over the course of the pregnancy. Finally, HRQoL was affected by mode of delivery., Conclusions: The results show that women and their husbands experienced marked changes in perceived health-related functioning and depressive symptoms during and after pregnancy. In addition, the study found that those women who had undergone Cesarean section had higher mental well-being scores. Future research should determine the benefits of extending pre-conception and pre-natal guidelines on the benefits of regular physical activity throughout and after pregnancy in Persian couples.