AbstractGlobal ocean O2 content has varied significantly across the eons, both shaping and being shaped by the evolutionary history of life on planet Earth. Indeed, past O2 fluctuations have been associated with major extinctions and the reorganization of marine biota. Moreover, its most recent iteration-now anthropogenically driven-represents one of the most prominent challenges for both marine ecosystems and human societies, with ocean deoxygenation being regarded as one of the main drivers of global biodiversity loss. Yet ocean deoxygenation has received far less attention than concurrent environmental variables of marine climate change, namely, ocean warming and acidification, particularly in the field of experimental marine ecology. Together with the lack of consistent criteria defining gradual and acute changes in O2 content, a general lack of multifactorial studies featuring all three drivers and their interactions prevents an adequate interpretation of the potential effects of extreme and gradual deoxygenation. We present a comprehensive overview of the interplay between O2 and marine life across space and time and discuss the current knowledge gaps and future steps for deoxygenation research. This work may also contribute to the ongoing call for an integrative perspective on the combined effects of these three drivers of change for marine organisms and ecosystems worldwide.