A catastrophic injury is a severe injury to the spine, spinal cord, or brain. It may also include skull or spinal fractures. This is a subset of the definition for the legal term catastrophic injury, which is based on the definition used by the American Medical Association.

The National Center for Catastrophic Sport Injury Research in the United States classifies catastrophic injuries based on the three outcomes associated with them: fatality, those causing permanent severe functional disability, and those causing severe head or neck trauma with no permanent disability. A fatal injury may be a direct result of trauma sustained during an activity or may occur indirectly. The indirect nonfatal catastrophic injury may occur as a result of systemic failure from exertion during an activity, such as from cardiovascular conditions, heat illness, exertional hyponatremia, or dehydration, or a complication to a nonfatal injury. Indirect fatalities are usually caused by cardiovascular conditions, such as hypertrophic cardiomyopathy and coronary artery disease.

Fatal injury may reveal an unknown "underlying anatomical, or physiological abnormality". Individuals with certain anatomical anomalies should not participate in some activities. For example, contact sports are contraindicated for individuals with an anomalous odontoid process, as any violent impact may result in a catastrophic injury. This is because a malformed odontoid process may lead to instability between the atlas and axis (the C1 and C2 cervical vertebrae). Those with atlanto-occipital fusion should also avoid contact sports.

Participation in any sport or recreational activity may result in a catastrophic sports injury, particularly if unsupervised or if engaged with little or no protection. Direct fatalities in sport are rare, as most sport fatalities are indirect and associated with non-sport cardiovascular problems.

In the United States, American football has the greatest incidence of catastrophic injury per population, whereas cheerleading is associated with the greatest incidence of direct catastrophic injury at both the interscholastic and intercollegiate levels.

Cervical spine trauma is most common in sports and activities involving contact and collision, particularly American football, rugby, ice hockey, gymnastics, skiing, wrestling, and diving. A 2005 report by the National Center for Catastrophic Sport Injury Research in the United States stated that sports requiring attention for potential catastrophic injuries are American football, ice hockey, baseball, wrestling, gymnastics, and track and field.

The incidence of catastrophic injury is four times higher in college than in high school in the United States. Sport accounts for between 5% and 10% of all cervical spine and spinal cord injuries in the United States, and 15% in Australia. The incidence of catastrophic injury for all sports is low, less than 0.5 per 100,000 participants.

A study in the province of Ontario in Canada based on epidemiological data from 1986, 1989, 1992, and 1995 states that the greatest incidence of catastrophic injuries occurred in snowmobiling, cycling, ice hockey, and skiing. Of the 2,154 reported catastrophic injuries, 1,756 were sustained by males and 368 by females. The only activity in the study in which female casualties outnumbered males was equestrianism. The study also stated that field and floor sports had a relatively low incidence of catastrophic injury, and that July had the highest incidence of injury. Drowning was the cause of 357 fatalities, and there were 640 head and 433 spine injuries.