Persistent dumping of sawdust on water banks and or directly into water bodies as a consequence of sawmilling activities is becoming alarming. This study therefore evaluated the effect of sawdust extract on some selected physiological parameters such as histopathology and oxidative stress response using O. niloticus as test organism. O. niloticus were divided into four groups based on exposure concentration to sawdust extract (0%, 1/10, 1/100 and 1/1000 of LC50 respectively) in triplicates. Heavy metals composition was evaluated using Atomic Absorption Spectrophotometer. Phytochemical analysis of sawdust, physico-chemical studies of the cultured water, histopathological and antioxidant enzyme activities were carried out using standard methods. Result showed the presence of metals such as iron, cadmium, zinc, copper and magnesium as well as the presence of alkaloids, flavonoids, steroid, phenols, terpenoid, saponin and anthraquinone in the sawdust extract. There was no significant difference in the water temperature and pH of the cultured water of O. niloticus exposed to the varying concentrations of the sawdust. Dissolved oxygen was however highest in the control water and reduced with increase in the concentrations of sawdust extract exposure. Disintegrated lamella was observed in the intestine and gills, and graded necrosis, in the liver of O. niloticus exposed to sawdust extract. There were inhibitions in the activities of superoxide dismutase (SOD) of both liver and kidney of O. niloticus exposed to sawdust extract. Activity of malondialdehyde (MDA) however, increased with increased extract concentration. This study has therefore shown that sawdust extract could cause tissue - organ architectural distortions and induce oxidative stress in O. niloticus.