Microalgae can be used as natural feed supplements for protecting fish protection against heavy metals toxicity.The present study investigated the effect of a mixture of heavy metals (Zn, Cu, & Pb) on Oreochromis niloticus fish and the potential protective roles of the microalgae “Chlorella vulgaris and Spirulina platensis" against heavy metals toxicity for 35 days.UponThe results showed that the addition of 10 & 15% of C. vulgaris and S. platensis in fish diets, an improvement was detected inimproved the hematological parameters (RBCs, WBCs, Hb, Ht, MCV, MCH, & MCHC) of fish exposed to heavy metals.Our resultsindicated that Meanwhile, sseveral histopathological alterations were observed in the gills, liver, intestine and muscles of fishas a result of heavy metals accumulation in these orgains. However, a decrease On the other hand,was recorded  in the histopathological changes regarding the examined tissues of heavy metals-treated fish upon usingC. vulgaris and S. platensis decreased the histopathological changes in the examined tissues of heavy metals-treated fish.In additionAlso, C. vulgaris and S. platensis showed a marked reduction in the bioaccumulation of Zn, Cu, & Pb in the liver, intestine, and muscles. Besides, C. vulgaris and S. platensis decreased the immunohistochemical expression of the proinflammatory cytokine “tumor necrosis factor alpha (TNF-α)" and increased the expression of the proliferative protein (ki-67) in the examined tissues of the exposed fish. It was deduced Our results concluded that, C. vulgaris and S. platensis in fish diets provided protection against heavy metals induceingd hematotoxicity, immunotoxicity and hisopathological alterations of O. niloticus fish.