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Codium fragile is an edible seaweed in Asian countries that has been used as a thrombolytic, anticoagulant, antioxidant, anti-inflammatory, and immune-stimulatory agent. Ginseng has also been known to maintain immune homeostasis and to regulate the immune system via enhancing resistance to diseases and microorganisms. In this study, anionic macromolecules extracted from C. fragile (CFAM) were orally administered with red ginseng extract (100 mg/kg body weight) to cyclophosphamide-induced immunosuppressed male BALB/c mice to investigate the immune-enhancing cooperative effect of Codium fragile and red ginseng. Our results showed that supplementing CFAM with red ginseng extract significantly increased spleen index, T- and B-cell proliferation, NK cell activity, and splenic lymphocyte immuneassociated gene expression compared to those with red ginseng alone, even though a high concentration of CFAM with red ginseng decreased immune biomarkers. These results suggest that CFAM can be used as a co-stimulant to enhance health and immunity in immunosuppressed conditions. KCI Citation Count: 0