AbstractTo predict the ecological consequences of expected global change, we need to understand the independent and combined effects of multiple stressors. Multiple experimental treatments are required to simultaneously test for effects of multiple stressors at different levels of intensity, independently and combined, and at different levels of biological organization. Most marine multiple stressors studies to date are conducted on assembled communities in mesocosms with a low number of treatments or low replication of treatments or both. These limitations prevent (1) robust data analyses, (2) characterization of single and combined effects of multiple stressors, and (3) identification of mechanisms underpinning biological responses. We present a new mesocosm‐based experimental platform for benthic communities: Quantifying the Impacts of Multiple Stressors (QIMS). Here, 96 independent mesocosms facilitate multifactorial and multilevel experimental designs with the high replication required for robust tests of multiple stressors and biological interactions. For example, three distinct pH levels are achieved by manipulating CO2 concentrations in the air supply, and three water temperature levels are provided by a cooling system in a fully crossed design that is required to identify all potential interactions, from which all combinations can be replicated 10 times (i.e., 90 experimental units). We demonstrate clearly how different levels of temperature and pCO2/pH can be manipulated precisely and maintained for at least 7 weeks. QIMS complements the limited number of permanently installed marine mesocosm facilities worldwide that simulate ocean warming and/or acidification and expedites multiple stressor research by providing an unprecedented level of replication for statistical robustness.