Legal restrictions and consumer trends are contributing to the growing movement for fish welfare. Therefore, the aquaculture sector is a means of reducing animal stress and enhancing physiological state, which raises financial profits. Feed additives have therefore been suggested as possible dietary stress alleviation. In this trend, a 75-day feeding trial was conducted to evaluate the effects of three organic acids (formic acid (FA), lactic acid (LA), and commercial organic acids mix (COM)) as dietary additives in Nile tilapia (Oreochromis niloticus) reared under a stressful condition (unchanged water). Fish (weighing 3.95 ± 0.05 g) were randomly housed into eight groups (n = 210 fish/group; 70 fish/replicate; 3 replicates/ group). The first (negative control) and second (positive control) groups were fed a basal diet without additives and with water exchange at 20% of the water volume every 2 days for the first group and without water exchange for the second. The other six groups (FA1, FA2, LA1, LA2, COM1, and COM2) were fed basal diets supplemented with OAs at two doses (1 and 2%) without water exchange during the trial. The results revealed that fish kept without water exchange (positive control) had the highest level of water-unionized ammonia and nitrite and a marked decline in growth performance (weight gain and specific growth rate). The unchanged water induced substantial decreases in the hematological profile (white and red blood cell count, hemoglobin value, and hematocrit %), protein profile indices (total protein, albumin, and globulin), and antioxidant-immune response (superoxide dismutase, catalase, lysozyme, and total immunoglobulin M). In addition, the biochemical indices (glucose, creatinine, urea, alanine aminotransferase, and aspartateaminotransferase) and lipid peroxide (malondialdehyde) were substantially increased in the positive control group. In addition to that, marked and severe histopathological alteration in the gills, liver, and intestine including hyperplasia, hemorrhage, and degenerative and necrotic changes that were associated with desquamation and sloughing were obvious in the PC group. Dietary LA1 significantly enhanced (P < 0.05) the overall measured indices; meanwhile, the dietary FA and COM recorded the worst results. Overall, our findings demonstrate that the unchanged water negatively affected the growth and physiological functions of Nile tilapia. Dietary incorporation of organic acids did not protect the fish from these hazards except the LA (1%). The latter can reduce nitrogenous compounds, enhance immune response, and alleviate these alterations for the sustainable aquaculture industry.