This study evaluated biochemical responses of genetically male tilapia after replacing fish oil with plant-based oils in their diets. The sources of oils were coconut, olive, crude palm, sunflower and sesame seed. These oils were incorporated at 7% level and were used to formulate five isonitrogenous (42.5% CP) diets. In the control experiment (sixth diet) fish oil was used. Fish were reared in 1 m x 1 m x 1 m floating net-hapa. Feeing trial lasted for 12 weeks. At the end of the experiment, blood samples were collected and tested for serum protein, electrolytes and tissue lipid peroxidation. Results of the study revealed that the ratio of albumin to globulin was statistically similar (p > 0.05) in all fish group examined. The results of serum electrolyte showed that olive oil treated fish recorded the highest (p < 0.05) level. The amount of malondialdehyde (MDA) formed in fish tissues increased (p < 0.05) in sunflower oil group by 69%, 43%, 20% and 32% in the liver, kidney, gills and heart respectively. This indicated that reactive oxygen species may be associated with the metabolism of sunflower oil leading to peroxidation of membrane lipids of the respective organs. However, this level of MDA deposition had not been associated with any negative effects on fish health. Inferences from this study conclusively support the direct use of these plant oils as total replacement for fish oil in diets of Oreochromis niloticus.