The aim of the present investigation was to obtain evidence, for the first time in red tilapia (Oreochromis spp.) on the effect of salinity 0 (T1), 10 (T2) and 20 ppt (T3) on the metabolism of glycogen in brain and liver, after the food intake. The fish (150 ± 10 g of weight) were obtained in the Tilapia production farm, TILAPAC-Honduras. They were placed in a battery of 6 experimental tanks (ET) for each salt concentration, n = 8. Prior to the experiment, the fish were not fed for 48 hours (h). Subsequently, the fish were anesthetized using MS-222. The brain and liver samples were taken and frozen at -30 ° C for the evaluation of glycogen levels from 0 h to 20 h with an interval of 4 h, between samples (1 ET = 4 h). The results show that at 0 and 10 ppt of salinity, glycogen levels increase in the liver at 4 and 12 h, respectively; while in the brain the increase was observed at 16 h postprandial (0 and 10 ppt) and at 12 h in 20 ppt. The fish at 20 ppt of salinity showed lower levels of liver glycogen than those placed at 0 and 10 ppt at 0, 4, 16 and 20 h postprandial; while in the brain this phenomenon was only observed at 4 and 8 h. There is a correlation between the fluctuation of glycogen levels throughout the experimental period between 0 and 10 ppt of salinity, in the liver (R: 0.85, P = 0.03) and brain (R: 0.994, P = 0.00005). Finally, the low levels of hepatic glycogen in 20 ppt of salinity suggest the probable activation of the HPI and HPC axes for the maintenance of osmoregulation. Therefore, tilapia cultivated in 20 ppt could present stress levels higher than those cultivated at 0 ppt and 10 ppt salinity.