The aim of this study is to investigate the effect of natural and experimental fasciolosis in sheep on some blood parameters including oxidative stress as thiobarbituric-acid reactive substances (TBARs) and some liver function tests as alanine amino transferase (ALT), aspartate amino transferase (AST), gamma glutamyl transferase (GT), lactate dehydrogenase (LDH) and blood bilirubin, as well as non-enzymatic antioxidants vitamin C. For this purpose, fifty sheep were divided into three groups, the 1st group (20 sheep) includes naturally infected sheep, the 2nd group (10 sheep) includes experimentally infected sheep and the 3rd group (20 sheep includes the control non-infected ones. Serum liver function tests (S-ALT, S-AST, S-YGT, S-LDH and bilirubin as well as oxidative stress indicators TBARs and vitamin C) were analyzed. The results revealed that both naturally and experimentally infected sheep showed highly significantly (p < 0.01) increased ALT, AST, YGT and LDH enzyme activities in serum. Moreover, serum bilirubin level was elevated in comparison with control group. Data indicated that TBARS level was significantly higher (p < 0.05) in naturally and experimentally infected than control sheep, while serum vitamin C level was significantly (p < 0.05) lower in both naturally and experimentally infected sheep than control ones. It could be concluded that changes in the oxidative stress of infected sheep were accompanied with rising activities of S-ALT, S-AST, S-YGT and S-LDH as markers of liver and gall bladder damage.