Abstract Background: Sodium benzoate (SB) is incorporated in many food and pharmacological manufacturing as a preserv-ative. Fructose (FR) is used a as substitute for sugar in many food products. Aim of Study: To test the cumulative effect of the combined daily use of SB and FR on rats' liver. Material and Methods: Twenty-four young male rats were assigned into four groups: 1- Control group; 2- SB group; 15mg/kg/day; 3- FR group; 10ml of 10% fructose/day; and 4- Combined SB +FR group. The rats were followed-up for 28 days. At day 28, animals were sacrificed and blood samples were drawn for liver enzymes analysis. The livers of the rats were divided into two parts; a part for freezing for homoge-nization and hydrogen peroxide analysis and the other for histopathological assessment. Results: The liver enzymes showed insignificant changes compared to the control group. The H2O2 was significantly elevated in SB and SB + FR groups. The liver architecture was negatively affected as detected by hematoxylin and Eosin, periodic acid Schiff and proliferating cells antigen stains. Conclusion: The combined use of SB and FR lead to detrimental effects on the liver function and structure. This in turn warrant cautious use of these substances and raise questions about the safety of using them in a combination on daily basis.