Stocking densities and long term zero culture water exchange rate effects, on biological performances, hematological and serum biological indices of Genetically Improved Farm Tilapia (GIFT) strain cultured in tanks were investigated. The trial was divided into four groups with three replicates each, conducted under natural photoperiods for 30 days; data were analysed using one way ANOVA. Results showed that, high stocking densities and zero water exchange rate negatively affected the biological performances, hematological and serum biochemical indices of GIFT tilapia juveniles. Feeding efficiency, specifc growth and survival rates were significantly decreased. Hematoogical indices: red blood cells, white blood cells, Hemoglobin, Hematocrit and platelet decreased as stocking density increased. Indices of liver function (Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) activities) were significant increased. Serum glucose levels, an indicator of cortisol released in blood were increased as stocking density increased. Meanwhile, total protein, triglyceride, cholesterol, triiodothyroxine, thyroxine levels in the blood serum showed downward regulation under the same experimental conditions. This paper would provide useful scientific knowledge on biological performances and physiological responses of GIFT strain tilapia to stressors like high stocking density and zero water exchange. Research with different fish sizes and water exchange rates should be further conducted.