Background: Sucralose and saccharin-cyclamate mixture are considered as safe commercial artificial sweeteners with many health authorities instead of natural sugar. We aimed to reveal their effects on the physiological, immunological and histological profiles. Methods and results mg/ml) in drinking water for 8 and 16 weeks. Only sucralose caused a temporary significant increase in blood glucose after 8 weeks that was eliminated after 16 weeks. WBCs count was decreased significantly after 16 weeks of sucralose administration. Aspartate aminotransferase creatinine (Cr) recorded an increase at 8 and 16 weeks due to the two artificial sweeteners intake. Both artificial sweetener induced a significant increase in interleukin (IL (LPS) levels with a progress from 8 th to 16 damage in kidney, liver, pancreas and urinary bladder. saccharin-cyclamate mixture, their chronic bladder. Moreover, they may interrupt the intestinal barriers leading to an cytokine secretions.