This study analyzed histopathological (gill lesions) and hematological (erythrocyte abnormalities) changes in tambaqui (Colossoma macropomum) in order to evaluate the water quality of fish farms in the Environmental Protection Area (EPA) of Maracanã, Maranhão, Brazil. Specimens of tambaqui were captured in two areas of EPA: A1) Serena Lagoon, and A2) River Ambude, in two seasonal periods, rainy and dry. For the hematological analyses, slides were made from the blood smear collected from the branchial arch of the fish. In the laboratory, the gills of each specimen were fixed in 10% formalin and maintained in 70% alcohol until the usual histological technique. The branchial changes were more frequent during the dry season in both areas. In the fish collection in A2, the following changes were noted: mucosal cells (78%), lamellar fusion (90%), lamellar disorganization (100%), lamellar narrowing (100%), and epithelial displacement (96%). In the fish collection in A1, the main lesions were: aneurysm (88%), dilation of the capillaries (82%), rupture of the capillaries (60%). In addition, nuclear alterations, such as binucleate cells (BC), cells with an evaginated nucleus (CEN) and cells with a lobulated carved nucleus (CLCN), were observed in the fish from both areas. The frequency of abnormalities was higher in the fish from A2 (74%) when compared to the fish from A1 (26%). In conclusion, we found that these alterations proved to be sensitive biomarkers capable of differentiating water quality and fish health status in the two systems in the Maracanã EPA.