The main aim of the present scientific paper is to assess water quality of the surface water of various lakes located in the Lumina-Rosu interdistributary depression, Danube Delta, Romania. As specific objectives, the paper considered to spot the main potential sources of contamination and their environmental impacts on aquatic ecosystems. Equally, the purpose of the article is to emphasize the importance of monitoring the water quality of the Danube Delta, for preserving these unique natural water resources and their ecosystem services (fresh water, biodiversity, flood control, recreation, nutrient cycling, fishing and other traditional activities, ecotourism). Surface water samples collected from several control sections situated on the main tributaries and canals, as well as from lakes were investigated physically (To - C, EC - μS/cm, TDS - mg/L, turbidity - NTU units, TSS - mg/L) and chemically (pH - units, DO - mg/L, N-NO2- - mg/L, N-NO3- - mg/L, P-PO43-- mg/L, Chla - mg/L, SiO2 - mg/L, TOC - mg/L, SO42- - mg/L, S2- - mg/L, H2S - mg/L and synthetic detergents - mg/L). Generally, the hydro-physical-chemical characteristics and water quality assessment of the surface waters of the lakes manifest the combined effect of both processes occurred in the catchment (weathering, sediment supply and transport), as well as the in situ lake processes (photosynthesis, sediment mixing, biogeochemical cycling, evaporation, eutrophication, productivity changes). Overall, the physical and chemical characteristics of the sampling sites investigated at high waters of the Danube are quite similar to those measured at low waters. The differences that mainly occurred within the lakes are more related to the limnological variables and the local environmental conditions. Anyway, a significant seasonal variation was noticed in the lakes, during the dry period, when different physical and chemical characteristics appeared to be influenced by high air temperature, lack of precipitation, low water level regime, low dissolved oxygen level regime, all related to climate change effects etc. Moreover, the anthropogenic factor that left its mark on some physical-chemical characteristics of water should not be omitted either. However, the results obtained within this study did not show such alarming values as might have dangerous effects on the investigated aquatic environments. The water quality information within this case study may be used for improving the understanding of the water quality issues and to better coordinate and plan for future monitoring activities in and around the Danube Delta environment. The results will contribute to updating the existing database with relevant information for a sustainable future of the Danube Delta and in similar areas that are subjected to such environmental challenges.