Edku lagoon is one of the important aquaculture sectors in the Nile Delta of Egypt. Recently, the lagoon has become a sink of discharge wastewater from different anthropogenic sources. The present work aims to study physicochemical parameters, level of nutrients and heavy metal concentrations in water of the lagoon to assess the water quality and identify the potential pollution source(s). Water quality index (WQI), eutrophication index and multiple heavy metal pollution indices (HPI, HEI, PI and C_d) in addition to evaluation of human health risk (HQ_dermal) model were applied. The obtained data revealed that physicochemical parameter varied between 7.62 - 8.90 for pH, 1.2 – 12.2 g/l for salinity, 3.5 – 12.5 mg/l for dissolved oxygen, 1.3 – 1.9 mg/l for ammonia, 0.065 – 0.191 mg/l for nitrite, 0.217 – 0.915 mg/l nitrate, 0.198 – 0.527 mg/l for orthophosphate, and 51.32 – 102.7 μg/l for chlorophyll-a. The average concentrations of heavy metals were 0.439, 0.322, 0.290,      0.328,     0.059,     0.040, 0.00005 ppm for Fe, Mn, Zn, Cu, Pb, Cd and Hg, respectively. Based on WQI, the lagoon was classified as bad water, while EI result varied between eutrophic to mesotrophic.  The pollution indices revealed to lagoon water is highly contaminated based on HPI, HEI and C_d and varied between slightly affected to seriously affected by heavy metals according to PI. Human health risk showed that, HQ_dermal for all metals except Cd lower than the unity.