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Median lethal concentration (LC50 − 96h), risk assessment, development, and mortality of Nile tilapia Oreochromis niloticus larvae exposed to oxytetracycline (OTC) after stress management were evaluated in this study. Fish (n = 126; 32.25 ± 3.74 mg; 13.01 ± 0.64 mm; 7 larvae/aquarium) were used for LC50 − 96h trial and randomly distributed in 21 aquaria (1 L) with 0.0, 2.01, 2.44, 3.31, 3.65 and 4.59 mg/L of OTC. For acute stress test, fish (n = 180; 33.9 ± 0.73 mg; 13.06 ± 0.72 mm; 10 larvae/aquarium) were submitted to air stress for 5 minutes and posteriorly randomly allocated in 18 aquaria (1 L) and exposed to 0.0, 0.03, 0.82, 1.65, 2.47 and 3.30 of OTC. Temperature, pH, dissolved oxygen (DO), conductivity, total ammonia and total hardness were measured daily. LC50 − 96h of OTC for Nile tilapia larvae was 3.45 mg/L. Weight and length of larvae submitted to graded levels of OTC decrease in both tests. Significant differences was observed for DO over 96h. pH, temperature and DO differ (P < 0.05) in post-stress test. Stress management (exposure to air) potentiates the toxic effects of sub-lethal doses of OTC. Furthermore, based on the risk quotient, OTC has a high risk to Nile tilapia larvae when exposed to therapeutic concentrations.