Introduction: Among the most prevalent psychiatric turmoils and the problems in human life, exhibit depression. Women are suffering from depression overmuch predominately than men and frequently cluster in the childbearing years. For women with pre-existing psychiatric ailments, Gestation and postnatal periods are large hazard times comparatively. This work designed to explore potential relation between depression and the fluctuation in the level of hormones and neurotransmitters. Methods: In the current work, ninety-five women aged 18-40 years consented to participate. They were allocated into three groups, which were as follow: Healthy non pregnant females (1st, control group), pregnant women during the third trimester (36-39 weeks) of gestation (2nd group) women in the early (1-2 days) postpartum period (3rd, group). Using a self-report questionnaire, we surveyed all eligible women at the Maternity and Children's Hospital in Azizia in Jeddah City. Depressive symptoms were accomplished by the help of Edinburgh Postnatal Depression Scale, Arabic version during the same period. After an overnight fast, blood samples were withdrawn for inspect of hormones (estrogen, progesterone and prolactin), neurotransmitters (Dopamine, Serotonin and Norepinephrine). Results: Pregnancy and postpartum groups exhibited significant increment in estrogen, progesterone, prolactin and norepinephrine levels accompanied by significant decline in dopamine and serotonin versus control group. Conclusion: It is clear that depression in late pregnancy and postpartum associates with some psychosocial, socioeconomic, neurotransmitters and hormonal variables.