Haloperidol is an antipsychotic and neuroleptic drug for treatment of symptoms of schizophrenia and other neuroleptic conditions. The study investigated the effects of haloperidol on peripheral erythrocytes and brain neurotransmitter levels of juvenile Clarias gariepinus. Clarias gariepinus juveniles were exposed to different concentrations of haloperidol (0.12, 0.24 and 0.48 mg/L) for 15 days and subsequently withdrawn from the drug for 5 days. Blood samples from the fishes on days 1, 5, 10, 15 and on the 5‐day withdrawal periods were analysed for mutagenic changes, after which the fish were sacrificed. The brain was sampled for serotonergic and dopaminergic analyses. There was formation of micronuclei in the peripheral fish blood which increased as the duration and concentrations of the drug increased. The drug significantly reduced the serotonin activity but increased dopamine activity. Some of the studied parameters, however, recovered from the effects of the drug after the 5‐day withdrawal period. Haloperidol is toxic to fish and its use in the environment should be guarded to avoid adverse impacts on non‐target species like fish.