This study aimed to determine the median lethal concentration (LC50) of total ammonia and nitrite's combined effect for Macrobrachium amazonicum and Macrobrachium rosenbergii post-larvae at 96 h of exposure and then present their safety levels. In the trial 640 post-larvae of M. amazonicum (2.2 ± 0.2 cm and 0.08 ± 0.02 g) and 640 post-larvae of M. rosenbergii (2.2 ± 0.3 cm and 0.07 ± 0.02 g) were distributed in a completely randomized 4 × 4 factorial design, consisting of four concentrations of total ammonia (0, 11, 22 and 44 mg.L−1 NH4Cl) and four concentrations of nitrite (0, 0.5, 1.5 and 3 mg.L−1 NaNO2) with four replicates for each treatment. All total ammonia concentrations were combined with all nitrite concentrations. According to the LC50 96 h obtained from the combined compounds, the safety levels for both species were determined, being 2.39 mg.L−1 of total ammonia and 0.14 mg.L−1 of nitrite for M. amazonicum. In contrast, for M. rosenbergii, the value was 2.50 mg.L−1 of total ammonia and 0.15 mg.L−1 of nitrite. Moreover, the additivity index demonstrated that, when combined, the compounds have an antagonistic effect on prawns. Additionally, considering the results obtained for both species, it was concluded that M. rosenbergii is more resistant to the combined effect of total ammonia and nitrite than M. amazonicum under the experimental conditions evaluated.