AbstractMicrobial growth and carbon use efficiency (CUE) are central to the global carbon cycle, as microbial remains form soil organic matter. We investigated how future global changes may affect soil microbial growth, respiration, and CUE. We aimed to elucidate the soil microbial response to multiple climate change drivers across the growing season and whether effects of multiple global change drivers on soil microbial physiology are additive or interactive. We measured soil microbial growth, CUE, and respiration at three time points in a field experiment combining three levels of temperature and atmospheric CO2, and a summer drought. Here we show that climate change-driven effects on soil microbial physiology are interactive and season-specific, while the coupled response of growth and respiration lead to stable microbial CUE (average CUE = 0.39). These results suggest that future research should focus on microbial growth across different seasons to understand and predict effects of global changes on soil carbon dynamics.