BURULLUS Lagoon, also known as Lake Burullus, is a brackish water lake in the Nile Delta in Egypt. In this study, changes in environmental conditions were assumed to affect phytoplankton species composition and their biochemical structure. The biochemical content of phytoplankton in Lake Burullus was preliminarily explored. Winter cruises were compared with summer cruises from 12 sites representing the main eastern, middle, and western lake basins in 2018. Results revealed that phytoplankton exhibited seasonal variations. In particular, it attained the lowest value in winter (72300 units/L) and the highest value in summer (88700 units/L). This observation was consistent with the high total protein content (2692.5mg/L) in summer. The first major class was Chlorophyceae (37.9%) followed by Bacillariophyceae (29.31%) and Cyanophyceae (20.7%). By comparison, Euglenophyceae and Dinophyceae were rare classes constituting 8.63% and 3.4%, respectively. The maximum total biochemical contents were found in the middle of the lake in winter (870.5, 57.6, and 6.1 mg/L of proteins, carbohydrates, and lipids, respectively), indicating the increase in the total density of phytoplankton, especially Chlorophyceae (13700 units/L), in the central basin (29200 units/L). The optimum total biochemical structure was obtained in the western basin in summer (1909.1, 55.4, and 6.5mg/L of proteins, carbohydrates, and lipids, respectively), suggesting that the phytoplankton density increased to 56000 units/L. Q index showed that the middle and western basins were in mesotrophic to eutrophic states. These findings demonstrated that excessive nutrient loads of drainage water into Burullus Lagoon significantly affected the phytoplankton biodiversity. Therefore, highly efficient management strategies must be developed and implemented in Burullus Lagoon.