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Harmful algal blooms (HABs), harmful microorganisms (pathogens) and toxic metals represent three major agents of water quality deterioration. Water quality of three northern lakes (Sardis, Enid, and Grenada) and a central lake (Ross Barnett Reservoir) of Mississippi, USA were examined in this study. While all these lakes are heavily used for recreational purposes, the Ross Barnett Reservoir serves additionally as the primary water supply for the City of Jackson, the capital city of Mississippi. The main goal of this study was to comprehensively assess the water quality of these lakes employing field and satellite data, and evaluate the potential human and aquatic health impacts. A time-series of true color images derived from satellite data indicated that algal blooms have been a recurring phenomenon in these lakes. Cyanobacteria, the algal group that predominantly occur in freshwater and form toxic blooms, were always present in these lakes and were most abundant on many occasions. The most toxic cyanotoxin, microcystin-LR, was found in all lakes, and its concentrations exceeded federal drinking water guidelines for children under six years of age many times. Potential bioaccumulation and biomagnification of microcystin-LR may pose serious risk to the aquatic ecosystem and human health including adults. Nutrient measurements indicated that all four lakes were eutrophic. Among bacterial populations, total coliforms and enterococci exceeded guideline values on several occasions. Arsenic, cadmium, chromium, and lead were found in the water of all the lakes, with arsenic exceeding the guideline values at two sites in Ross Barnett Reservoir. While it is apparent from this study that these lakes face many water quality issues, data across all seasons will be required to document potential trends and to devise management strategies. Use of remote sensing technology is recommended to monitor some of the water quality parameters such as suspended particulate matter and algal blooms, especially cyanobacterial blooms.