A study was conducted in June 2009 to assess the current status of ecological condition and potential human-health risks throughout subtidal estuarine waters of the Sapelo Island National Estuarine Research Reserve (SINERR) along the coast of Georgia. Samples were collected for multiple indicators of ecosystem condition, including water quality (dissolved oxygen, salinity, temperature, pH, nutrients and chlorophyll, suspended solids, fecal coliform bacteria and coliphages), sediment quality (granulometry, organic matter content, chemical contaminant concentrations), biological condition (diversity and abundance of benthic fauna, fish tissue contaminant levels and pathologies), and human dimensions (fish-tissue contaminant levels relative to human-health consumption limits, various aesthetic properties). Use of a probabilistic sampling design facilitated the calculation of statistics to estimate the spatial extent of the Reserve classified according to various categories (i.e., Good, Fair, Poor) of ecological condition relative to established thresholds of these indicators, where available.