In a field study conducted for 102 days at feeding period, using a polyculture system (Nile tilapia, silver carp, common carp, and African catfish at a rate 1: 1: 1: 1) in two Hapas, one for control fish fed a commercial diet and the second one fish were fed a dried sewage sludge (DSS, product of treating sanitary and agricultural drainage of Al-Reiad, Kafr El-Sheikh, Egypt). At the end of the experiment, blood samples were withdrawn and liver samples were taken from each fish species for hematological, biochemical and histological examinations. From the obtained results, it was clear that DSS feeding did not negatively affect the blood picture in general, although the significantly elevated values of transaminases activity and triglycerides concentration. DSS feeding led to some drastic histological alterations in the liver structure. Conclusively, and because of the presence of some pollutants from agricultural and urban drainages whether in the rearing water or in the sewage sludge that can negatively affect fish health, production, and quality as well as could be inter the food chain and threat human health; so, it is recommended to give more concern on food and water quality (environmental friendly) used in aquaculture to offer safe products for human consumption.