The objective of this study is to develop a Pollution Early Warning System (PEWS) for efficient management of water quality in oyster harvesting areas. To that end, this paper presents a web-enabled, user-friendly PEWS for managing water quality in oyster harvesting areas along Louisiana Gulf Coast, USA. The PEWS consists of (1) an Integrated Space-Ground Sensing System (ISGSS) gathering data for environmental factors influencing water quality, (2) an Artificial Neural Network (ANN) model for predicting the level of fecal coliform bacteria, and (3) a web-enabled, user-friendly Geographic Information System (GIS) platform for issuing water pollution advisories and managing oyster harvesting waters. The ISGSS (data acquisition system) collects near real-time environmental data from various sources, including NASA MODIS Terra and Aqua satellites and in-situ sensing stations managed by the USGS and the NOAA. The ANN model is developed using the ANN program in MATLAB Toolbox. The ANN model involves a total of 6 independent environmental variables, including rainfall, tide, wind, salinity, temperature, and weather type along with 8 different combinations of the independent variables. The ANN model is constructed and tested using environmental and bacteriological data collected monthly from 2001 – 2011 by Louisiana Molluscan Shellfish Program at seven oyster harvesting areas in Louisiana Coast, USA. The ANN model is capable of explaining about 76% of variation in fecal coliform levels for model training data and 44% for independent data. The web-based GIS platform is developed using ArcView GIS and ArcIMS. The web-based GIS system can be employed for mapping fecal coliform levels, predicted by the ANN model, and potential risks of norovirus outbreaks in oyster harvesting waters. The PEWS is able to inform decision-makers of potential risks of fecal pollution and virus outbreak on a daily basis, greatly reducing the risk of contaminated oysters to human health.