Infectious diseases with complications of sepsis are still public health concern in both developed and developing countries. Sepsis is a potentially life-threatening systemic immune response to infection that can lead to end- stage organ failure and death. Sepsis involves multiple mechanisms such as neuroendocrine, complement activation, blood coagulation, and fibrinolytic system. Reactive oxygen species (ROS) is an inflammatory mediator produced by NADPH oxidase activation. This study aimed to investigate the effects of ethanol extract of E. elatior fruits on NADPH oxidase activity. Forty Mus musculus mice were randomized divided into five groups (n=8), with the intervention group receiving an intraperitoneal injection of 0.3 mg/kg BW lipopolysaccharide (LPS). There was a normal group without LPS injection (N-1), LPS injection only (N-2), and those that received LPS injection and ethanol extracts of E. elatior fruits containing 2.1 mg/20 g (N-3), 4.2 mg/20 g (N-4), and 8.4 mg/20 g (N-5). NADPH oxidase activity were measured using ELISA. The oneway ANOVA was used to investigate the differences between the groups. After administration of the extract at a varied dose, N-5 group the lowest NADPH oxidase activity (p=0.001). The ethanol extract of E. elatior fruit has antioxidant effects. In this study, a dose of 8.4 mg/20 g of extract significantly reduced NADPH oxidase activity. The ethanol extract of E. elatior might be considered a treatment in sepsis.