During the summer of 2016, the ongoing New England drought reduced flows in many streams and rivers to their lowest levels in more than 50 years. Drought conditions cause a myriad of environmental changes in rivers and streams including increased temperature, decreased oxygen levels, and increased concentration of many solutes due to evaporation. Surprisingly, how extremely low flows impact ecosystem function in river networks is not well understood. To address this knowledge gap, we deployed a network of in situ water quality sondes to measure ecosystem metabolism. Ecosystem metabolism is a measure of oxygen consumption by heterotrophic metabolism and gross primary production is oxygen produced by autotrophic processes within a river reach. We hypothesized that the extreme drought conditions would have a negative impact on aquatic biota in streams and rivers, resulting in decreased respiration and primary production rates. Data were collected from May 2015 through January 2017 using probes deployed in channels across the Connecticut River watershed including sites in the Farmington River (Connecticut; n=8) and Passumpsic River (Vermont; n=8) watersheds. Contrary to our hypothesis, in smaller streams and rivers metabolic rates did not increase or decrease significantly in response to drought. By contrast, in the main stem of the Connecticut River both primary production and respiration rates increased greatly as drought conditions deepened. Increased residence time in the Connecticut River during low-flow conditions allowed a robust planktonic microbial community to develop. This microbial community was responsible for high primary production rates that produced large amounts of organic carbon. This organic carbon was then released to the river environment, stimulating high levels of microbial heterotrophy. Metabolic rates in the Connecticut River main stem were generally elevated, but also highly variable, indicating that extreme drought conditions can drive ecosystem instability in large river systems.