Copper (Cu) belongs to a class of heavy metals that play an essential part as a cofactor in cellular metabolism, participating in the metabolism of the respiratory chain and iron. It becomes harmful to fish above a certain concentration when its concentration reaches that of the biological requirement. Fish blood is prone to contamination and xenobiotic may be used as toxicity indexes for its alternation. This study was conducted to demonstrate the effect of copper sulfate (CuSO4) on hematological and immunological parameters of African catfish with or without garlic extract incorporation into fish feed. Materials and methods: The experiments were carried out in four groups comprising 20 fish in each group, African catfish, Clarias gariepinus. The results declared signs of anemia in the copper sulfate treated group that represented in a significant decrease of RBCs, Hb content, PCV%, MCV, WBCs, lymphocytes, eosinophils, and immunological parameters, while a significant increase in MCHC values, heterophils, and monocytes when compared with the corresponding control group. For garlic extract supplemented groups either alone or in combination with copper sulfate treatment, there was a significant increase in RBCs, Hb, PCV%, MCV, WBCs and modulating the deranged differential leukocyte count and phagocytic activity as well as a serum level of nitric oxide, lysozyme activity and IgM due to copper toxicity. The hematology and immunity of C Gariepinus can be affected negatively by CuSO4, causing numerous health and well-being disruptions. The introduction of garlic into fish feed has been found to enhance hematological parameters and immune-competent cell activity in this species, with increasing infection tolerance indicating the enhanced efficacy of garlic against the immunologic effects of CuSO4 in fish. (c) 2020 Elsevier B.V. All rights reserved.