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Streptococcus agalactiae and Streptococcus iniae are the two main pathogens causing streptococcosis in fish. This study compares the clinicopathological changes in red hybrid tilapia experimentally infected with S. agalactiae or S. iniae. A total of 180 tilapias were divided into six groups. Groups 1A, 2A, and 3A were inoculated intraperitoneally with sterile phosphate-buffered saline, S. agalactiae, and S. iniae. Fish of Groups 1A, 2A, and 3A were then immediately allowed to cohabitate with fish of Groups 1B, 2B, and 3B, respectively. All fish were observed at 6-hr intervals for 120 hr before surviving fish were euthanized. The spleen, liver, and brain samples were collected for bacterial isolation and histopathology. Clinical signs were developed at 72 hr in Groups 2A and 3A and 96 hr in Groups 2B and 3B. Group 2A showed the highest clinical score (P< 0.05). Significantly (P< 0.05), more cohabitating fish (Groups 2B) were infected by S. agalactiae compared to S. iniae (Group 3B) at 55.0±0.0 and 43.70±1.25%, respectively. The mortality rate was significantly (P< 0.05) higher for Groups 2A and 2B than other groups. The gross lesions were significantly (P< 0.05) more common in fish of Group 2A. Histopathologically, encephalitis was observed in fish infected