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Background: Artificial sweeteners interfere with normal physiological processes. Objective: The study aims at assessing the changes associated with consuming different doses of aspartame (Sugar-Match®) and sucralose (Sweetal®). Methods: A total of sixty rats were divided into two phases; phase I was categorized into 6 groups including a control group, sucralose 2 and 4 g/kg, aspartame 0.8 and 1.6 g/kg, and sucrose with dose 0.5 mg/kg given orally every day for 12 weeks. Rats were euthanized and lipid profile was measured. Phase II comprised 4 groups including the same previously mentioned doses of sucralose and aspartame which were given orally every day for 12 weeks then omitted for further 6 weeks to study the ability of body to restore the biological changes associated with their consumption. Results: The highest triglyceride level was observed in rats fed on high dose sucralose (80.83 ± 5.46 mg/dl) and aspartame (78.83 ± 4.17 mg/dl). After 12 weeks of experimentation, cholesterol was higher in all groups. LDL-C was the highest in rats supplemented with a high dose of aspartame (43.90 ± 8.41 mg/dl), followed by a low dose of aspartame (39.28 ± 2.03 mg/dl). Terminating intake of artificial sweeteners caused large drop in LDL-C in rats fed on high dose of aspartame, while HDL-C increased slightly but insignificantly. Severe histopathological changes in liver and kidney tissues were observed in rats supplemented with a high dose of aspartame. Conclusion: Supplementing rats with aspartame and sucralose for 12 weeks increased lipid profile. Pathological changes were recovered neither in the liver nor in the kidney even after terminating artificial sweeteners intake.