End stage kidney disease contributes to a huge burden on global health. Recent advances have shown that ischemic and hypoxic conditions may contribute to the progression of the disorder and that acute kidney injury may cause and aggravate the condition. Ischemia and hypoxia are two distinct conditions with different pathophysiological and structural consequences as proven in the brain and liver of rats. Until now, these differences have not been shown to exist in the kidney. In this study, we assess the possible functional differences in the outcome of ischemic and hypoxic stress on the kidney. For this purpose, we perfused isolated rabbit kidneys with their autologous blood and applied short periods of ischemia or hypoxia in separate series of experiments. The results showed that the kidneys exposed to hypoxic stress suffered more functional damage than those subjected to ischemia. This conclusion was based on a lower creatinine clearance and urine osmolality, and a higher fractional excretion of urea, sodium, and glucose in the hypoxia series of kidneys. Consequently, we recommend monitoring hypoxemic conditions closely and correcting the condition as soon as possible, since even for a short period it may already have deteriorating effects on the renal function.