Object There are increasing levels of global cadmium (Cd 2+ ) aquatic environmental pollution with untold consequences following either sudden exposure to large concentrations or prolong exposure to low doses. The investigation of sudden exposure to large concentrations of Cd 2+ toxicities in exposed fish, especially in the hardy and adaptable Clarias gariepinus (C. gariepinus) with accessory breathing organs will further elucidate on its toxicity pathways given the spates of industrial accidents-induced environmental pollution. Methods The experiment involved the use of 126 adult C. gariepinus exposed to various concentrations of cadmium chloride (CdCl 2 ) over a 96-h period, in triplicates, following 14-day acclimatization period. Results Initial behavioral agitations progressed to depression, including signs of respiratory distress, neurotoxicity, and death in some of the exposed fish. A median lethal concentration (LC 50 ) established for CdCl 2 was 10.48 mgL −1 in the exposed adult C. gariepinus. The exposure caused sudden deterioration in fish water quality with severe gill cellular damage, which provoked variable hematological responses in the exposed fish. Conclusion Cadmium chloride was more toxic to C. gariepinus adults than already reported for C. gariepinus fingerlings and juveniles based on the established LC 50 values. Sudden exposure to large concentration of CdCl 2 has the propensity to negatively impact fish health indirectly (changes in fish water quality) and directly (hemotoxicity and cellular damages).