Ediacaran fossils document the early evolution of complex megascopic life, contemporaneous with geochemical evidence for widespread marine anoxia. These data suggest early animals experienced frequent hypoxia. Research has thus focused on the concentration of molecular oxygen (O2) required by early animals, while also considering the impacts of climate. One model, the Cold Cradle hypothesis, proposed the Ediacaran biota originated in cold, shallow-water environments due to increased O2 solubility. First, we demonstrate using principles of gas exchange that temperature does have a critical role in governing the bioavailability of O2 – but in cooler water the supply of O2 is actually lower. Second, the fossil record suggests the Ediacara biota initially occur ~571 Ma in deep-water facies, before appearing in shelf environments ~555 Ma. We propose an ecophysiological underpinning for this pattern. By combining oceanographic data with new respirometry experiments we show that in the shallow mixed layer where seasonal temperatures fluctuate widely, thermal and pO2 effects are highly synergistic. The result is that temperature change away from species-specific optima impairs tolerance to low pO2. We hypothesize that deep and particularly stenothermal (narrow temperature range) environments in the Ediacaran ocean were a physiological refuge from the synergistic effects of temperature and low pO2.