Recent studies suggested that virological response of Hepatitis C Virus to treatment might be lower insulin resistance (IR) and lipid profile abnormalities, but the extent of their impact on treatment response has not been established. The aim of this study was to confirm the role of IR and lipid profile abnormalities on virological response of chronic hepatitis C infected patients and to determine its magnitude. Eighty non-hypertensive, non-cirrhotic Saudi patients with chronic HCV infection; Patients were divided in to two equal groups according to their blood level profile and insulin resistance levels: Group (A):  Included HCV patients with normal lipid profile and non-diabetic without insulin resistance. Group (B): Included HCV patients with high Triglycerides, Total cholesterol and LDL & non-insulin dependent diabetic with insulin resistance. There were significant differences between both groups regarding Total cholesterol, Low density lipoprotein, High density lipoprotein, insulin resistance and virological response. The Pearson’s correlation coefficients test for the relationship between virological response and Total cholesterol, Low density lipoprotein, High density lipoprotein, insulin resistance in both groups showed a strong direct relationship in both groups. While, there was a strong inverse relationship between virological response and High density lipoprotein in both groups. Insulin resistance and lipid profile abnormalities adversely affect virological response to treatment of Hepatitis C Virus.