This research was carried out at Microbiol. Lab., Faculty of Agric., Damietta Univ. to evaluate the water and fish of River Nile. Water and fish samples were collected from the same site of River Nile in Damietta governorate namely Farskour city during spring, summer, autumn and winter at 2014. All fishes obtained from Rive Nile were belonging to one genus of fish namely, Oreochromis niloticus (Nile tilapia). Long, weight and color of examined fish were recorded. Temperature, electrolyte conductivity (EC) and dissolved oxygen (DO) of River Nile water were determined. Obtained results proved that the highest value of Biochemical Oxygen Demand (BOD5) was found during winter being 7.0 mgO2/L and the lowest value was during summer being 4.7 mgO2/L. Cadmium was detected in summer, autumn and winter 0.001, 0.003 and 0.007, respectively. In case of spring these minerals were not detected. The highest value of total bacteria, total fungi, staphylococci, Aeromonas and coliform count in the water were 6.121, 4.231, 4.342, 3.301 and 5.997 log cfu/ml, respectively. The highest values of bacterial groups of muscles, intestine and surface of fish were in spring and the lowest values were in autumn. Twenty bacterial isolates were identified; 2 colonies were considered as Staphylococcus sp., other 2 were considered as Micrococcus sp. Six colonies were considered as Bacillus sp. Another five colonies were considered as Aeromonas sp. Three fungal isolates were identified as Aspergillus oryzae.