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Abstract Sepsis is an inevitable stage of bacterial invasion characterized by an uncontrolled inflammatory response resulting in a syndrome of multiorgan dysfunction. Most conventional antibiotics used to treat sepsis are efficacious, but they have undesirable side effects. The green synthesised Ag NPs were synthesized by 5 g of the earthworm extract dissolved in a volume of 500mL of distilled water and then added to 2,500 mL aqueous solution of 1mM silver nitrate at 40 °C. After 4 h, the mixture was then allowed to dry overnight at 60 °C. Later, Ag NPs were washed and collected. They were characterized by X-ray diffraction, ultraviolet-visible spectroscopy, and transmission electron microscopy. Sepsis model as induced by feces-intraperitoneal injection method. Eighteen male mice were assigned into three main groups: the control group, the sepsis-model group, and the Ag NPs-treated group. The control group received a single oral dose of distilled water and, after two days, intraperitoneally injected with 30% glycerol in phosphate buffer saline. The Sepsis-model group received a single oral dose of distilled water. Ag NPs - The treated group received a single oral dose of 5.5 mg/kg of Ag NPs. After two days, the sepsis-model group and Ag NPs-treated group were intraperitoneally injected with 200 µL of faecal slurry. Ag NPs treatment in septic mice significantly decreased liver enzyme activities, total protein, and serum albumin. Moreover, Ag NPs significantly enhanced kidney function, as indicated by a significant decrease in the levels of creatinine, urea, and uric acid. In addition, Ag NPs showed a powerful antioxidant effect via the considerable reduction of malondialdehyde and nitric oxide levels and the increase in antioxidant content. The histopathological investigation showed clear improvement in hepatic and kidney architecture. Our findings demonstrate the protective efficacy of biogenic Ag NPs against sepsis-induced liver and kidney damage.