An asphyxiant gas, also known as a simple asphyxiant, is a nontoxic or minimally toxic gas which reduces or displaces the normal oxygen concentration in breathing air. Breathing of oxygen-depleted air can lead to death by asphyxiation (suffocation). Because asphyxiant gases are relatively inert and odorless, their presence in high concentration may not be noticed, except in the case of carbon dioxide (hypercapnia).

Toxic gases, by contrast, cause death by other mechanisms, such as competing with oxygen on the cellular level (e.g. carbon monoxide) or directly damaging the respiratory system (e.g. phosgene). Far smaller quantities of these are deadly.

Notable examples of asphyxiant gases are methane, nitrogen, argon, helium, butane and propane. Along with trace gases such as carbon dioxide and ozone, these compose 79% of Earth's atmosphere.

Asphyxiant gases in the breathing air are normally not hazardous. Only where elevated concentrations of asphyxiant gases displace the normal oxygen concentration does a hazard exist. Asphyxiant gases are marked SA in the NFPA 704 standard. Examples of hazards are:

The risk of breathing asphyxiant gases is frequently underestimated leading to fatalities, typically from breathing helium in domestic circumstances and nitrogen in industrial environments.

The term asphyxiation is often mistakenly associated with the strong desire to breathe that occurs if breathing is prevented. This desire is stimulated from increasing levels of carbon dioxide. However, asphyxiant gases may displace carbon dioxide along with oxygen, preventing the victim from feeling short of breath. In addition the gases may also displace oxygen from cells, leading to loss of consciousness and death rapidly.

The handling of compressed asphyxiant gases and the determination of appropriate environment for their use is regulated in the United States by the Occupational Safety and Health Administration (OSHA). The National Institute for Occupational Safety and Health (NIOSH) has an advisory role. OSHA requires employers who send workers into areas where the oxygen concentration is known or expected to be less than 19.5% to follow the provision of the Respiratory Protection Standard [29 CFR 1910.134]. Generally, work in an oxygen depleted environment requires an SCBA or airline respirator. The regulation also requires an evaluation of the worker's ability to perform the work while wearing a respirator, the regular training of personnel, respirator fit testing, periodic workplace monitoring, and regular respirator maintenance, inspection, and cleaning." Containers should be labeled according to OSHA's Hazard Communication Standard [29 CFR 1910.1200]. These regulations were developed in accordance with the official recommendations of the Compressed Gas Association (CGA) pamphlet P-1. The specific guidelines for prevention of asphyxiation due to displacement of oxygen by asphyxiant gases is covered under CGA's pamphlet SB-2, Oxygen-Deficient Atmospheres. Specific guidelines for use of gases other than air in back-up respirators is covered in pamphlet SB-28, Safety of Instrument Air Systems Backed Up by Gases Other Than Air.

To decrease the risk of asphyxiation, there have been proposals to add warning odors to some commonly used gases such as nitrogen and argon. However, CGA has argued against this practice. They are concerned that odorizing may decrease worker vigilance, not everyone can smell the odorants, and assigning a different smell to each gas may be impractical. Another difficulty is that most odorants (e.g., the thiols) are chemically reactive. This is not a problem with natural gas intended to be burned as fuel, which is routinely odorized, but a major use of asphyxiants such as nitrogen, helium, argon and krypton is to protect reactive materials from the atmosphere.