Statins are the preferred therapy to treat hypercholesterolemia and decrease coronary heart disease. However, previous studies have reported mitochondrial dysfunctions of several experimental models submitted to diverse statins treatments. The aim of the present study was to investigate whether treatment with doses of pravastatin during 3 months induces hepatotoxicity in LDL receptor knockout mice (LDLr-/-), a model for human familial hypercholesterolemia. We evaluated liver mitochondrial function parameters, antioxidant enzymes activities and protein and lipid oxidation markers. We observed a higher mitochondrial H2O2 production rate, decreased activity of aconitase and increased MPT. Among several antioxidant enzymes, only G6PD activity was increased in treated mice. The presence of several oxidized lipid species was detected in pravastatin group but protein oxidation markers were not altered. Diet supplementation with the antioxidants CoQ10 or creatine fully reversed all pravastatin effects. Taken together, our results show that pravastatin chronic treatment induced liver mitochondrial redox imbalance that may explain the hepatic side effects reported in a small number of patients, and the co-treatment with safe antioxidants neutralize these side effects.