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An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge Geodia barretti . This includes three new metabolites, namely geobarrettin A⁻C ( 1 ⁻ 3 ) and four known compounds, barettin ( 4 ), 8,9-dihydrobarettin ( 5 ), 6-bromoconicamin ( 6 ), and l-6-bromohypaphorine ( 7 ) . The chemical structures of compounds 1 ⁻ 7 were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A ( 1 ) was assigned by ECD analysis and Marfey's method employing the new reagent l- N α -(1-fluoro-2,4-dinitrophenyl)tryptophanamide (l-FDTA). The isolated compounds were screened for anti-inflammatory activity using human dendritic cells (DCs). Both 2 and 3 reduced DC secretion of IL-12p40, but 3 concomitantly increased IL-10 production. Maturing DCs treated with 2 or 3 before co-culturing with allogeneic CD4⁺ T cells decreased T cell secretion of IFN-γ, indicating a reduction in Th1 differentiation. Although barettin ( 4 ) reduced DC secretion of IL-12p40 and IL-10 (IC 50 values 11.8 and 21.0 μM for IL-10 and IL-12p40, respectively), maturing DCs in the presence of 4 did not affect the ability of T cells to secrete IFN-γ or IL-17, but reduced their secretion of IL-10. These results indicate that 2 and 3 may be useful for the treatment of inflammation, mainly of the Th1 type.