Ethidium bromide (EtBr) is one of the contaminants recorded in aquatic environments whose effects have been investigated; however, there is still limited knowledge about its remediation. This study examined the potential protective effects of Spirulina platensis (SP) against the effects of EtBr toxicity in the Nile tilapia (Oreochromis niloticus) fry. Fry were divided to five groups, viz., a control and four treatment groups of low-dose EtBr (10 μg/ L), low-dose EtBr with SP (10 μg/L EtBr + 200 mg/L SP), high-dose EtBr (100 μg/L), and high-dose EtBr with SP (100 μg/L EtBr + 200 mg/L SP); the exposure period was 2 weeks. Low and high doses of EtBr induced alterations in some hematological, biochemical, and histopathological parameters. Necrotic hepatocytes, degenerated area, vacuolated hepatocytes, pyknotic nuclei, constricted and dilated blood sinusoids, and infiltration of in-flammatory cells were observed. Lipid peroxidation concentration was not significantly different in groups exposed to low doses of EtBr and EtBr with SP, but it was increased in groups exposed to high doses of EtBr and EtBr with SP, compared with the control group. After feeding with SP, most histological and histochemical parameters restored to normal values. Therefore, SP may possess the ability to preserve the structural integrity of the he-patic and renal membranes.