Background: Postpartum depression (PPD) is a global childbirth-related problem that affects many women and if ignored can have long-term adverse consequences, for both mother and child. Therefore, timely identification of its risk factors requires a good knowledge base for the care provider. Methods: A descriptive cross sectional study was used to assess the knowledge of PPD and its associated risk factors among nurse-midwives in a tertiary hospital in Bayelsa State, Nigeria. A systematic random sampling technique was used to select a sample size 114 nurse-midwife respondents. A well-structured questionnaire was used to collect data from the participants. The same were analyzed using descriptive and inferential statistics with level of significance was set at 0.05(5%). Findings: Despite the fact that majority of nurse-midwives rated their information level on postpartum depression as moderate, most of them still maintained that cigarette smoking, unwanted pregnancy, poor economic status cannot predispose a woman to PPD. Furthermore, majority affirmed that Edinburg Postnatal Depression Scale (EPDS) can be used to screen for PPD yet only about half of the respondents opined that PPD tendency can be detected during pregnancy and less than half of them affirmed that a score of > 10 using the EPDS indicates depression. The study also found significant relationship between educational qualification and level of information about PPD and its associated risk factors. Conclusion: The level of knowledge of nurse-midwives is not at the expected level since majority still have knowledge deficit regarding risk factors and how to detect PPD. Hence, it was recommended that periodic suitable training programs on PPD should be developed for healthcare professionals especially for nursemidwives who are the first point of contact during antenatal, labour and post-natal period.