Aquaponics is an eco-friendly system that integrates soilless cultivation and aquaculture. This study aimed to assess the water quality, hematological and biochemical parameters, and growth performances of tilapia (Oreochromis niloticus), as well as Lettuce (Lactuca sativa) yield, reared for 110 days in a newly developed deepwater culture (DWC), as a prototype built in the Upper Egypt Center of Development owned by the Academy of Scientific Research and Technology (ASRT) in Sohag Governorate, Egypt. The experimental work consisted of two DWC systems. Fish (n= 300 with an average weight (18 ± 0.8 g)) were fed daily for five days a week with 2% of the total biomass with a protein feed content (30%). The results showed that water quality parameters were within the optimal range for tilapia culture except for pH. The hematological and biochemical parameters and growth performances were within typical values. The growth and yield of Lettuce were measured through fresh weight, and they were better than in other studies. Aquaponics technology can be used to produce high-quality tilapia and lettuce.