Copper (Cu) is an essential trace metal in aquatic environments. However, excess Cu can induce toxic effects at levels of biochemical and histopathological aspects. Previous studies have reviewed the importance of spirulina supplementation in neutralizing the harmful influences of heavy metals in various fish species. In the present work, the biochemical and histopathological effects of 0.4 and 0.8mg/ l of Cu were addressed on Oreochromis niloticus fed spirulina-free diet (SFD) or spirulina-supplemented diet (SSD). Hepatic protein content showed a highly significant increase in fish exposed to 0.8mg/ l of Cu and fed SSD for 7 days. On the 14^th day, a significant increase in lipid content was noticed in the liver of fish exposed to 0.8mg/ l of Cu and fed SFD. Both protein and lipid content showed a significant increase in the liver of fish fed SSD without Cu exposure. On the 7^th day, a significant increase was found in the liver glycogen of fish exposed to 0.4mg/ l of Cu and fed SFD. While, on day 21, a highly significant increase was found in the liver glycogen concentration in fish exposed to 0.4mg/ l of Cu and fed SSD. Cu induced many pathological lesions including vacuolar degeneration, pyknosis and degenerative and necrotic changes till the loss of architecture and hemorrhagic lesions. The liver histopathological changes observed were more evident with high Cu concentrations and time. The impact of sublethal concentrations of copper on O. niloticus is intense. The role of 1% spirulina platensis supplementation was limited in neutralizing the harmful influences of Cu on O. niloticus