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Background: Approximately 10 to 20% of pregnant women worldwide experience perinatal depression (PND), a depressive episode with onset during pregnancy or after childbirth. We performed a systematic review to identify, summarize and discuss studies on inflammatory biomarkers described in relation to PND. Methods: Inclusion criteria defined the selection of observational studies written in English, French, Spanish or Portuguese, that evaluate analytical levels of inflammatory molecules (protein levels) in biological fluids in women, with a diagnosis of depression using ICD/DSM diagnostic criteria or depressive symptoms assessed by standardized psychometric instruments, during pregnancy and/or postpartum. Case reports, experimental studies, reviews, qualitative analysis, meta-analysis, gray literature or replicated data were excluded. Three electronic databases were used for search (Pubmed, Web of Science and PsychInfo) and quality assessment of selected studies were performed using the Newcastle-Ottawa Scale. Data extraction included study design; number of subjects; obstetric information; tools and timepoints of depression and inflammatory markers assessment. Results: 56 studies where the major aim was to analyze the association between depression and inflammatory biomarkers during pregnancy and postpartum period were included in this systematic review. Overall, the findings of our systematic review lend support to the hypothesis that several inflammatory markers may be associated with peripartum depressive symptoms. The associations were somewhat different looking at pregnancy compared to the delivery time-point and postpartum, and mainly referred to increased levels of IL-6, IL-8, CRP and TNF-α among depressed. Discussion: Our results revealed high heterogeneity in relation to the timing of biological sampling for markers, as well as timing and instruments used for depression assessment within the perinatal period for the different studies. Studies differed also in relation to use of biomarkers or depression as exposure and outcome respectively, and whether these were addressed at the same timepoint or separate ones. Given the high burden of PND on women, children and families, it is crucial to try to harmonize methods used in related studies, in order to be able to pool results that could give us insights into the pathophysiological mechanisms behind how the immune system and PND are connected; this could have great impact on early detection, prevention and even treatment of PND.