After building the High Aswan Dame (HAD), flood water is stored in Lake Nasser. The biochemical composition of the phytoplankton community andmicrobial loadare considered as biomarkers of the ecosystem including water, sediments, plant and fish in different khors of Lake Nasser. So the present study investigated the variation of chlorophyll a in water of Dahmeit and Tushka Khors during high flood and drought seasons. Also, the total protein, carbohydrate and lipid contents of phytoplankton and the microbial load in water, sediment, macrophytes and fish in these Khors during high flood and drought seasons were investigated. Data of this study indicated that Tushka khor recorded higher yield of all biochemical contents of algae than Dahmeit khor during the two seasons. In addition, higher chlorophyll a and protein contents were recorded in surface layer than bottom one. Microbial analyses indicated that the total bacterial counts and the total diazotrophs were present in high population densities in all water samples at different seasons. Higher flooding season recorded higher autochthonous and allochthonous as well as higher diazotrophic bacteria than drought season for Tushka khor. Furthermore, Tushka Khor recorded higher nitrogen-fixing bacteria than dahmiet khor. Also, Tushka khor recorded slightly higher total sediment bacterial counts than Dahmeit khor. On the other hand, the highest bacterial load of various fish organs was recorded in Dahmeit khor compared to Tushka khor. Microbial analyses of macrophyte species included total bacterial counts, as well as total diazotrophs were present in high population densities in all sample at deferent seasons. This study provides evidence that the biochemical composition of phytoplankton as well as water and sediment quality and fish healthy and distribution of macrophytes is affected by the flood. Thus, great efforts and cooperation between different authorities are needed to regular evaluation and study Lake Nasser and its khors to protect them from pollution and reduce environmental risk.