There are projections of continuous increase in the world’s energy demand, which might result to increase in oil and gas exploration and production activities. Nigeria for instance, runs a mono-economy that largely depends on the revenues from her rich oil and gas deposits. Oil and gas exploration and production activities are expected to increase over the years in Nigeria to meet her economic needs, as well as the global energy need. However, oil and gas production activities are associated with environmental concerns, especially with respect to management of the kind of wastes it generates. A major waste generated during oil and gas completion and production operations is the Produced Water (composed of water, different production chemicals and other constituents). This study is focused on evaluation of the toxic effects of selected production chemicals on the Niger Delta freshwater Tilapia guineensis. Among the chemicals evaluated include: SPECTRUS NX1173 (Biocide), FLOGARD MS 6208 (Corrosion inhibitor), ELIMINOX (Oxygen scavenger) and EC9017A (anti-foam), while Tilapia guineensis was used as the bioindicator. Whereas there are past researches on the individual chemicals and confirmation that they are toxic in nature, there are no adequate researches on the comparative toxicity effects of these chemicals, especially on the Niger Delta environment. Produced water samples were simulated in the laboratory using the production chemicals (at different concentrations) and 2000ml of freshwater sample for each experimental setup. The fishes were acclimatized for ten days using same freshwater sample, those that survived were selected for the experiment. The mortality and survival rate of the test organism was monitored at a constant interval of one (1) hour for Ninety-six (96) hours and the percentage mortality of the test organism recorded for all the chemicals at different concentrations ranged from 100% to 10%. The lethal concentration (LC50) calculated for each of the chemicals are as follows: Corrosion inhibitor 0.002%, biocide 0.003%, oxygen scavenger 0.01% and defoamer 0.176%. The corrosion inhibitor was the most toxic as there was 100% mortality of the Tilapia guineensis within 24 hours of the test period, while the defoamer was the least toxic as there were more survival of the test organism at the end of the test period. The test results indicated that all the production chemicals used in this research were toxic, their lethal concentrations differed from one chemical to the other, and the corrosion inhibitor and biocide had the highest toxicity effect on the organisms. The research findings could be used as a basis by the Nigerian regulatory agencies for possible review of currently approved completion and production chemicals for oil and gas activities, as well as produced water disposal options, especially discharge in water bodies in the Niger Delta.