The aim of the current study was to examine: 1) the relationship between a novel multi-protein derived measure of IL-6 activity/bioavailability and other relevant immune markers; 2) the relationship between IL-6 activity/bioavailability and inflammation-related clinical and cognitive outcomes in depression; and 3) how associations for this novel biomarker with depression outcomes compare to those for relevant single immune proteins, such as IL-6, CRP, and sIL-6R. Here, IL6 is linked to major depressive disorder.