Streptococcosis is one of the most important bacterial diseases of tilapia. The present study assessed the histopathological changes induced by Streptococcus agalactiae challenge in the brain, kidney, spleen, and liver of Oreochromis mossambicus. When challenged intraperitoneally at 10 7-10 8 cells/fish, S. agalactiae strains (TKT 1 and TBT 2) caused 40-100% mortalities in O. mossambicus. The LD 50 values of S. agalactiae TKT 1 and TBT 2 strains were 1.60×10 7 and 7.33×10 7 cells/fish, respectively. Histological sections of the challenged O. mossambicus brain exhibited meningoencephalitis, marginated haemocytes, extensive haemorrhages, oedema and neurons with marginated nuclei. The kidney of challenged tilapia showed glomerulopathy, dilation of Bowman's capsule, nephritis, haematopoietic tissue necrosis, melanization and granulomatous-like lesions. The spleen was characterized by extensive melanomacrophage aggregation, necrosis and vasodilation. The liver had dilated and ruptured blood capillary, melanization and disintegrated tissue. The intrahepatic exocrine pancreatic tissue was disintegrated. Our results demonstrated that S. agalactiae caused a systemic infection and meningoencephalitis in the Mozambique tilapia juveniles.