A survey was conducted to characterize the status of water quality (salinity, dissolved oxygen, pH, and temperature), eastern oyster (Crassostrea virginica) reproduction, and eastern oyster health in the St. Lucie Estuary (SLE), located near Stuart, Florida. The SLE receives water from an intensively drained watershed through a variety of interconnected swales, ditches, and canals. Specific indicators of oyster health and recruitment included condition index, gonadal index, spat settlement, and infection intensity of Perkinsus marinus. Water pH, salinity, DO, and temperature varied among locations and throughout the seasons. Temperatures were highest (31°C) from June through August and lowest (13°C) in January. Salinity, the most variable parameter, ranged from <1–30 ppt. Significant depressions in salinity were apparent during Lake Okeechobee discharge events through Canal-44 (C-44) and when long-duration rainfall events occurred within the immediate watershed and the Canal-23 (C-23) and Canal-24 (C-24) drainage basins. Measured DO was generally >2 mg L⁻¹ and pH ranged from 7–8.5. Spat settlement was always lower in the SLE as compared with reference sites in the Indian River Lagoon. The majority of spat settlement in the SLE occurred from April through June. Gonadal stage of oysters and condition index varied throughout the seasons. This survey will serve as a useful benchmark for measuring the success of future projects directed towards management of water quality and enhancement of oyster habitat in the SLE.