Energy production in the Williston Basin, USA, results in the coproduction of highly saline, sodium chloride-dominated water (brine). The Prairie Pothole Region (PPR) overlies the northeastern portion of the Williston Basin. Although PPR wetlands span a range of salinity, the dominant salt is sodium sulfate, and salinities are much lower than brine. Introduction of brine to wetlands can result in pronounced water-quality changes; however, the ecological effects of such contamination are poorly understood. We examined the effects of brine contamination on primary productivity, emergent macrophyte tissue chemistry, and invertebrate communities from 10 wetlands in the PPR. Based on a recognized Contamination Index (CI) used to identify brine contamination in the PPR, water-quality samples indicated that six wetlands were uncontaminated while four were contaminated. Across this gradient, we observed a significant decrease in above-ground biomass and a significant increase in tissue chloride concentrations of hardstem bulrush (Schoenoplectus acutus) with increased CI values. Additionally, a significant decrease in macroinvertebrate taxonomic richness with increased CI values was observed. These findings provide needed insight on the biological effects of brine contamination on PPR wetlands.