Hypoxia refers to low oxygen conditions. Hypoxia is problematic for air-breathing organisms, yet it is essential for many anaerobic organisms. Hypoxia applies to many situations, but usually refers to the atmosphere and natural waters.

Atmospheric hypoxia occurs naturally at high altitudes. Total atmospheric pressure decreases as altitude increases, causing a lower partial pressure of oxygen, which is defined as hypobaric hypoxia. Oxygen remains at 20.9% of the total gas mixture, differing from hypoxic hypoxia, where the percentage of oxygen in the air (or blood) is decreased. This is common in the sealed burrows of some subterranean animals, such as blesmols. Atmospheric hypoxia is also the basis of altitude training, which is a standard part of training for elite athletes. Several companies mimic hypoxia using normobaric artificial atmosphere.

An aquatic system lacking dissolved oxygen (0% saturation) is termed anaerobic, reducing, or anoxic.

In water, oxygen levels are approximately 7 ppm or 0.0007% in good quality water, but fluctuate. Many organisms require hypoxic conditions. Oxygen is poisonous to anaerobic bacteria for example.

Oxygen depletion is typically expressed as a percentage of the oxygen that would dissolve in the water at the prevailing temperature and salinity. A system with low concentration—in the range between 1 and 30% saturation—is called hypoxic or dysoxic. Most fish cannot live below 30% saturation since they rely on oxygen to derive energy from their nutrients. Hypoxia leads to impaired reproduction of remaining fish via endocrine disruption. A "healthy" aquatic environment should seldom experience less than 80% saturation. The exaerobic zone is found at the boundary of anoxic and hypoxic zones.

Hypoxia can occur throughout the water column and also at high altitudes as well as near sediments on the bottom. It usually extends throughout 20–50% of the water column, but depends on the water depth and location of pycnoclines (rapid changes in water density with depth). It can occur in 10–80% of the water column. For example, in a 10-meter water column, it can reach up to 2 meters below the surface. In a 20-meter water column, it can extend up to 8 meters below the surface.

Hypolimnetic oxygen depletion can lead to both summer and winter "kills". During summer stratification, inputs or organic matter and sedimentation of primary producers can increase rates of respiration in the hypolimnion. If oxygen depletion becomes extreme, aerobic organisms, like fish, may die, resulting in what is known as a "summer kill". The same phenomena can occur in the winter, but for different reasons. During winter, ice and snow cover can attenuate light, and therefore reduce rates of photosynthesis. The freezing over of a lake also prevents air-water interactions that allow the exchange of oxygen. This creates a lack of oxygen while respiration continues. When the oxygen becomes badly depleted, anaerobic organisms can die, resulting in a "winter kill".

Oxygen depletion can result from a number of natural factors, but is most often a concern as a consequence of pollution and eutrophication in which plant nutrients enter a river, lake, or ocean, and phytoplankton blooms are encouraged. While phytoplankton, through photosynthesis, will raise DO saturation during daylight hours, the dense population of a bloom reduces DO saturation during the night by respiration. When phytoplankton cells die, they sink towards the bottom and are decomposed by bacteria, a process that further reduces DO in the water column. If oxygen depletion progresses to hypoxia, fish kills can occur and invertebrates like worms and clams on the bottom may be killed as well.