The present study is a part of a cooperative project to enable the efficient transfer of innovative ecotechnology ASTAF-PRO aquaponic from Germany to Egypt for sustainable aquaculture and food production. The present part was carried out to evaluate the impact of ASTAF-PRO aquaponic system on water quality parameters and the health status of the monosex Nile tilapia Oreochromis niloticus. Water quality analysis revealed an improvement of most parameters in an aquaponic system with a significant reduction in toxic ammonia. In aquaponic, the nitrite level in ASTAF-PRO was lower than the permissible limit, probably because of the double-sided action of nitrobacteria present in the biological filters and the grow beds of the plant in the system. No significant difference was observed in the values of nearly all the hematological parameters in the blood of fishes reared in the aquaponic system and those reared in POND systems, being always within the normal ranges for the healthy Nile tilapia. Most of the measured biochemical variables exhibited an improvement in the blood of fish reared in the ASTF-PRO system compared to that of the POND. This suggests that fish health improved when reared in aquaponic with better water quality parameters. Immunoglobulin (IgM) levels and lysozyme activity were the same in the blood of fish reared in both systems, confirming that the monosex Nile tilapia was still fit with a good immunological status under aquaponic condition. In conclusion, the health status of the monosex Nile tilapia reared in ASTAF-PRO aquaponic system was better than those reared in POND in terms of hematology, biochemistry and immunological status. Obviously, the difference in the health status of fish in different systems can be linked to water quality since the same feed was used.