PURPOSE: Increased inflammation has been described as consistently associated with depression. Moreover, the pro-inflammatory pattern was found in women with a history of trauma irrespective of major depression diagnosis. In this study, we explored the possible association of inflammatory markers with perinatal depression (PND), measuring serum levels of cytokines (IL-6, TNF-a, IFN-γ), acute phase proteins (CRP), erythrocyte sedimentation rate (ESR), cortisol and brain-derived neurotrophic factor (BDNF) in women at the second trimester of pregnancy. Moreover, we tested whether the biological markers were correlated with the severity of PND, trauma history and resilience level. METHODS: Seventy-nine women including two groups of patients (women with PND at the second trimester of pregnancy with and without history of trauma) and two healthy control groups (inside and outside the peripartum) were enrolled. Blood sampling were collected for measuring putative biological markers. Clinical interview, Edinburgh Postnatal Depression Scale (EPDS), Inventory of Traumatic experiences (TEC), Connor-Davidson Resilience Scale (CD-RISC) were administered. RESULTS: Women with PND and trauma reported a higher EPDS (p=0.004) and lower CD-RISC scores compared to other groups (F=34.77; p<0.001). The one-way ANOVA analysis showed lower ERS (F=2.87; p=0.040), CRP (F42=4.05; p=0.010) mean values among PND women without trauma and higher TNF-α mean values (F=6.07; p=0.001) among PND women with trauma history compared to other groups. CONCLUSIONS: History of trauma was associated with a more severe clinical phenotype of PND and decreased resilience level. The increase of acute phase proteins in women with PND and higher TNF-a level in those with trauma exposure validated the inflammatory theory of PND. Our findings substantiated the need of implementing the screening of pregnant women with the assessment of trauma history. Properly, resilience-enhancing interventions are recommended with the aim of support mothers and mitigate the possible transgenerational transmission of pathology. The biological results are compelling although preliminary.