The immune system of the African sharptooth catfish (Clarias gariepinus) is analogous to that of other vertebrates, divided into innate and adaptive systems. Cadmium is a naturally occurring trace metal, present in different concentrations both in sediments and biota environments with some toxic effects. The toxicity of Cd ranges from subcellular to systemic effects, affecting also the immune system of organisms, depending on the dose and duration of exposure. In Tanzania, Cd has been reported in catfish from a sewage pond and aquaculture in Morogoro and Arusha. This experimental study investigated the effect of Cd on the innate immune response of the African Sharptooth catfish by assessing the peripheral blood cell population, cell fragility, and cellular changes in responses to infectious agents via phagocytosis The Cd concentrations of 0.03 ppm and 0.24 ppm were used over three weeks. With such Cd concentrations, Cd accumulated in tissues with notable effects on blood tissue and cell functioning. The white blood cell control results were stable within a narrow range (28.8 to 32.0) x 103 cells /mu l, while treatment results progressively decreased. The white blood cells ranged from 18.7 to 32.0 x 103 cells /mu l in week 1, 13.5 to 29.8 x 103/mu l cells in week 2 and 9.6 to 28.8 x 103 cells / mu l in week 3. The decrease of red blood cells was noted each week from 1.9 in week 1 to 1.2 x 106 cells / mu l in week 3, while the average Hb declined from 9.3 g/dl in week 1 to 5.0 g/dl in week 3. There was an in vitro decline in cellular fragility and impaired phagocytosis in Cd-exposed fish compared to the control, but without a significant difference in resistance to Aeromonas hydrophila infection. Microflora increased cell parameters in Cd unexposed cells, while Cd significantly impaired white blood cell abundance, cell fragility, and innate immunity functions.