Different ways have been used in an attempt to decrease the risk of aflatoxicosis in fish. This study was undertaken to compare the possible alleviative effects of hydrated sodium calcium aluminosilicate (HSCAS) and Saccharomyces cerevisiae against the toxic impact of aflatoxin B₁ (AFB₁) on Oreochromis niloticus (O. niloticus). Therefore, 180 normal cultured monosex O. niloticus were randomly allocated into 6 equal groups. Group 1, was received the basal ration only. Group 2, was fed a basal ration supplemented with 0.5% HASCAS. Group 3, was fed a basal diet enriched with 0.25% Saccharomyces cerevisiae. Group 4, was received a diet intoxicated with 2.5 ppm aflatoxin B₁. Group 5, was fed a diet intoxicated with 2.5 ppm AFB₁ with 0.5% HSCAS. Group 6, was fed a diet intoxicated with 2.5 ppm AFB₁ with 0.25% S. cerevisae. AFB₁ intoxication induced mortality 16.67 %, leucopenia, lymphopenia, neutrophilia with a significant decrease in phagocytic % and index. Furthermore, significant increases in serum creatinine, ALT and ALP as well as a significant decrease in total protein, albumin and globulin were recorded. Moreover, accumulation of aflatoxin residues in O. niloticus flesh (5 ppb) and liver (15 ppb). While, supplementation of AFB₁ intoxicated diet either with S. cerevisiae or HSCAS ameliorated the drastic effects of aflatoxin on O. niloticus and S. cerevisiae appear to be more effective in the protection of fish from aflatoxicosis than HSCAS.