Once an eruption occurs, a large CO₂ cloud forms above the lake and expands to the neighbouring region. Because CO₂ is denser than air, it has a tendency to sink to the ground while pushing breathable air up. As a result, life forms that need to breathe oxygen suffocate once the CO₂ cloud reaches them, as there is very little oxygen in the cloud. The CO₂ can make human bodily fluids very acidic, potentially causing CO₂ poisoning. As victims gasp for air they actually hurt themselves more by sucking in the CO₂ gas.

At Lake Nyos, the gas cloud descended from the lake into a nearby village where it settled, killing nearly everyone. In this eruption, some people as far as 25 km (15.5 miles) from the lake died. A change in skin color on some bodies led scientists to think that the gas cloud may have contained a dissolved acid such as hydrogen chloride as well, but that hypothesis is disputed. Many victims were found with blisters on their skin. This is believed to have been caused by pressure ulcers, which likely formed from the low levels of oxygen present in the blood of those asphyxiated by the carbon dioxide. Thousands of cattle and wild animals were also asphyxiated, but no official counts were made. On the other hand, vegetation nearby was mostly unaffected except for that which grew immediately adjacent to the lake. There the vegetation was damaged or destroyed by a 5-meter (16.4 ft.) tsunami from the violent eruption.