Endotoxemia (sepsis, septic shock) is an inflammatory, virulent disease that results mainly from bacterial infection. The present study investigates the inhibitory effect of a bioprocessed polysaccharide (BPP) isolated from the edible Lentinus edodes liquid mycelial mushroom culture supplemented with black rice bran against murine endotoxemia induced by the Salmonella lipopolysaccharide and d-galactosamine (LPS/GalN). BPP was obtained after dialysis against water using a cellulose tube with a molecular weight cutoff of 10000. BPP eluted as a single peak on an HPLC chromatogram. Acid hydrolysis of BPP showed the presence of the following sugars: fucose, galactose, galactosamine, glucose, glucosamine, mannose, rhamnose, and xylose. Treatment of BPP with β-glucanase reduced its immunostimulating activity, suggesting that the polysaccharide has a β-glucan structure. Pretreatment of mice with BPP via oral or intraperitoneal (ip) administration for 2 weeks resulted in the suppression of LPS/GalN-induced catalase, superoxide dismutase (SOD), and transaminase (GOT/GPT) liver enzymes, amelioration of necrotic liver lesions, and reduction of tumor necrosis factor α (TNF-α) and nitrite serum levels as well as myeloperoxidase (MPO) activity, an index of necrotic injury. Immunostimulating macrophage activity was up to 5.4-fold greater than that observed with the culture without the rice bran. BPP also extended the lifespan of the toxemic mice. These positive results with inflammation biomarkers and lifespan studies suggest that the BPP can protect mice against LPS/GalN-induced liver, lung, and kidney injuries and inflammation by blocking oxidative stress and TNF-α production, thus increasing the survival of the toxic shock-induced mice. The polysaccharide has the potential to serve as a new functional food.