Childhood maltreatment (CM) is associated with chronic low-grade inflammation and an increased risk for the development of adverse mental and physical health outcomes in CM-affected adults. Differences in cortisol signaling were described to contribute to this pro-inflammatory phenotype. We investigated in a study cohort of 13 postpartum women with and 12 postpartum women without CM whether treatment of peripheral blood mononuclear cells (PBMC) with cortisol, the anti-glucocorticoid hormone dehydroepiandrosterone (DHEA), or co-treatment with both differentially affected pro-inflammatory cytokine release ex vivo. The childhood trauma questionnaire was used to retrospectively assess CM and the severity of CM experiences (maltreatment load). PBMC of maltreated women (CM+) showed in all conditions an increase in pro-inflammatory cytokine secretion compared to PBMC of the control group (CM-), which was correlated with the maltreatment load. Ex vivo stimulation analyses provided preliminary evidence for a differential responsivity of PBMC in CM+ and CM- women to cortisol regarding TNF-α secretion, but no difference in the responsivity to DHEA treatment. The results of the co-treatment with cortisol and DHEA support the hypothesis that cortisol and DHEA interact in the modulation of inflammatory processes.