The estuarine ecosystems of southeastern Louisiana are threatened by numerous environmental impacts such as wetland loss, coastal development, and overharvesting of natural resources. If the relative health of different estuaries can be determined, then management efforts might be focused on those regions needing the most protection. Unfortunately, estuaries are by definition dynamic, precluding easy comparisons of relative environmental health. Meta-analyses can be used to overcome problems associated with this natural variability. Analyzing sizable ecological data sets that cover large spatial and temporal scales is helpful in assessing relative ecosystem health among different regions. To compare the health of four estuarine regions of southeastern Louisiana (the Barataria Basin, Lake Maurepas, Lake Pontchartrain, and the Biloxi Marsh and Chandeleur Islands region), we calculated taxonomic distinctness and variation in taxonomic distinctness for fishery-independent data collected from three habitats: demersal, nearshore, and pelagic habitats. Taxonomic distinctness is a biodiversity index that measures taxonomic distance between species collected in a single sample. This taxonomic-based method is robust to differences in sample size and generally more useful for large-scale meta-analyses than other diversity measures. We analyzed data collected by trawls (demersal habitats), beach seines (nearshore habitats), and gill nets (pelagic habitats) over various periods in the last half century. Demersal fish assemblages from Lake Pontchartrain and pelagic fish assemblages from the Barataria Basin were more affected than fishes collected in similar habitats in the other regions. Nearshore fish assemblages, though, were equally healthy across all regions studied.