Objective: To evaluate synergistic nootropic effect of low dose aspirin and Ondansetron in rats. Material and Methods: Retention of conditioned avoidance response was assessed using repeated electroconvulsive shock in rats. Electroconvulsive shock was used to induce amnesia. Rats were divided into five groups: control (pretreated with distilled water), Electroconvulsive shock (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s), combined Electroconvulsive shock and aspirin (7.5mg/kg) pretreated groups, combined Electroconvulsive shock and ondansetron (0.4 mg/kg) pretreated groups, combined Electroconvulsive shock, aspirin (7.5mg/kg) and ondansetron (0.2 mg/kg) pretreated groups. Data was analyzed by ANOVA followed by Dunnet__ampersandsignrsquo;s test. Result: Findings showed that administration of single Electroconvulsive shock daily for consecutive 8 days results in disruption of the retention of conditioned avoidance response. Ondansetron and aspirin significantly prevented Electroconvulsive shock -induced attenuation of the retention of conditioned avoidance response. Combined Aspirin and subnootropic dose of Ondansetron prevented Electroconvulsive shock - induced attenuation of the retention of conditioned avoidance response which is significantly higher than aspirin alone. Conclusion: This study concludes, Aspirin might inhibit this serotonergic transmission and results in its neuroprotective action. When aspirin is combined with 0.2 mg/kg of ondansetron, retention of CAR was significantly higher than aspirin alone.