The Loxahatchee National Wildlife Refuge (Refuge) is affected by inflows containing elevated contaminant concentrations originating from agricultural and urban areas. Water quality was determined using three networks: the Northern Refuge (NRN), the Southern Refuge (SRN), and the Consent Decree (CDN) monitoring networks. Within these networks, the Refuge was divided into four zones: (1) the canal zone surrounding the marsh, (2) the perimeter zone (0 to 2.5 km into the marsh), (3) the transition zone (2.5 to 4.5 km into the marsh), and (4) the interior zone (>4.5 km into the marsh). In the NRN, alkalinity (ALK) and conductivity (SpC) and dissolved organic carbon, total organic carbon, total dissolved solids (TDS), Ca, Cl, Si, and SO(4) concentrations were greater in the perimeter zone than in the transition or interior zone. ALK, SpC, and SO(4) concentrations were greater in the transition than in the interior zone. ALK, SpC, and TDS values, Ca, SO(4), and Cl had negative curvilinear relationships with distance from the canal toward the Refuge interior (r(2) = 0.78, 0.67, 0.61, 0.77, 0.62, and 0.57, respectively). ALK, TB and SpC, and Ca and SO(4) concentrations decreased in the canal and perimeter zones from 2005 to 2009. Important water quality assessments using the SRN and CDN cannot be made due to the sparseness and location of sampling sites in these networks. The number and placement monitoring sites in the Refuge requires optimization based on flow pattern, distance from contaminant source, and water volume to determine the effect of canal water intrusion on water quality.