Hematological parameters and changes in stress-induced functionalities of cellular enzymes have been recognized as valuable tools for monitoring fish health and determining the toxic effects of pesticides. The present study was conducted to evaluate the toxic effect of selected pesticides viz., Ekalux (EC-25%), Impala (EC-55%), and Neemstar (EC-15%) on freshwater catfish Mystus keletius. Fish were exposed to sub-lethal concentrations (mg/L) of the selected pesticide for a period of 7, 14, 21, and 28 days. Hematological parameters viz., total erythrocyte (RBC), hemoglobin (Hb), and hematocrit (Ht) packed cell volume values decreased with an increase in exposure time to pesticides, whereas the values for parameters viz., leucocytes (WBC), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) increased significantly. A decrease in packed cell volume (PCV) and hemoglobin values coupled with decreased and deformed erythrocytes as signs of anemia were also observed. The effect of pesticides on RBC content was 1.43 (million/mm³) on day 7 and reduced to 1.18 (million/mm³) on days 14 and 21. A similar trend was found for Impala on RBC, which had an initial value of 1.36 (million/mm³) on day 7 and reached a value of 1.10 (million/mm³) on day 28. In contrast, the value of Neemstar decreased from 1.59 (million/mm³) on day 7 in control to 1.02 (million/mm³) on day 28. Data indicates that the order of toxic effect of pesticides recorded a maximum for Impala followed by Ekalux and Neemstar in the selected fish model. Likewise, the overall pattern of pesticidal activity on cellular enzymes (GDH, MDH, and SDH) recorded a maximum toxic effect for Impala followed by Ekalux and Neemstar. Results indicate that Chlorpyrifos pesticide-Impala evoked maximum toxic effect on selected tissues compared to the other two pesticides tested. Statistical analysis of the summative data using two way ANOVA was statistically significant (p-value < 0.001). The differences in the hematological parameters analyzed are attributed to the physiological acclimatization of the fish to the local conditions, which influences the energy metabolism and consequently determines the health status of the fish. Overall, Impala exhibited the highest pesticidal activity on cellular enzyme, followed by Ekalux and Neemstar. Results suggest that natural pesticides may be preferable for rice field application in terms of environmental safety.