A study was conducted to evaluate the impact of acute sub-lethal toxicity of monocrotophos on behavioural, biochemical, haematological and histopathological changes in Heteropneustes fossilis (49.53±0.71 g). Probit analysis showed the 96 h LC 50 of monocrotophos for H. fossilis was 20 ppm. Followed by the LC 50 value, sub-lethal concentrations for acute exposure of monocrotophos were 3 ppm in T 1 , 6 ppm in T 2 and 8 ppm in T 3 for 72 h of the experimental period. The behavioural responses observed in treated fish were: erratic movement, imbalance in swimming, surfacing, and hyperactivities. A gradual reduction in total RBC count, haemoglobin, monocyte, and basophil contents were observed with an increased concentration of monocrotophos. On other hand, the total WBC count, neutrophil, basophil and blood ESR showed reversed trend (p<0.05). Total tissue protein content of gill, liver and kidney was altered and decreased significantly (p<0.05) in monocrotophos-treated fish. Tissue lipid peroxidation (LPO) and catalase activities in gill, liver and kidney were also altered after 24 h, 72 h and followed an increasing trend in exposed fish which differed significantly (p<0.05) from the control group. Compared to the control, significant changes were observed in the histopathological architecture of blood cells and gill tissue. The overall result showed that exposure to monocrotophos severely affects fish behaviour and physiology. Therefore the misuse of the chemical may be avoided to reduce the negative impact on aquatic animals.