The most common cause of fish kills is suffocation due to lack of dissolved oxygen. Most dissolved oxygen is produced by algae and aquatic plants through photosynthesis. A lesser but also important source of oxygen in water is diffusion from the atmosphere, which is enhanced by wind-induced surface water turbulence.

In both natural ecosystems and home aquariums, the single biggest cause of fish death is hypoxia (oxygen depletion). In the wild, "fish kills" occur when factors like extreme heat, droughts, or massive algae blooms strip the dissolved oxygen from the water faster than it can be replaced, essentially causing the fish to suffocate. In the home aquarium hobby, the most common cause is poor water quality, specifically high levels of ammonia and nitrite. This is often the result of "New Tank Syndrome," where the beneficial bacteria needed to break down waste haven't yet been established, or from overfeeding, which leads to rotting organic matter. Secondary causes include stress-induced parasites (like Ich or Velvet) and "osmotic shock" caused by improper acclimation to new water chemistry. While many hobbyists blame "old age" or diseases, most aquatic veterinarians agree that almost all captive fish deaths can be traced back to environmental instability that weakens the fish's immune system, making them vulnerable to pathogens that they would otherwise be able to fight off easily.