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The objectives of this research were to determine the median lethal concentration at 96 hours (LC5 -96 hr) of copper sulfate in Nile tilapia (Oreochromis niloticus) fry by static bioassay test, and to evaluate the toxicity of copper sulfate in the gills and skin of Nile tilapia fry. The fish were exposed to 0, 6, 12, 18, 24 and 30 mg/L of copper sulfate, respectively. The 96 hr LC value of copper sulfate was 6.671 mg/L. Histopathological changes of gill in the 50 treatment groups were focal hyperplasia in gill lamellae and caused lamellar fusion. Focal epithelial lifting and disarray of some gill lamellae were also observed. Furthermore, curling at the tips of some gill lamellae and colloid droplet deposited เท gill lamellae were occasionally found. Copper sulfate had no effect on skin histology of the treatment groups and no external lesions occurred. The epidermal thickness of the skin from the treatment groups showed non-significant difference from the control group (p>0.05). The results of this study may indicate the sensitivity of Nile tilapia fry to copper sulfate and the histopathology of the gills may be a tool to reveal the toxicity effect of copper sulfate เท the environment and aquatic biota. [ABSTRACT FROM AUTHOR]