Unintentional weight loss occurs in many diseases and conditions, including some very serious diseases such as cancer, AIDS, and a variety of other diseases.

Poor management of type 1 diabetes mellitus, also known as insulin-dependent diabetes mellitus (IDDM), leads to an excessive amount of glucose and an insufficient amount of insulin in the bloodstream. This triggers the release of triglycerides from adipose (fat) tissue and catabolism (breakdown) of amino acids in muscle tissue. This results in a loss of both fat and lean mass, leading to a significant reduction in total body weight. Note that untreated type 1 diabetes mellitus will usually not produce weight loss, as these patients get acutely ill before they would have had time to lose weight.

In addition to weight loss due to a reduction in fat and lean mass, illnesses such as diabetes, certain medications, lack of fluid intake and other factors can trigger fluid loss. Fluid loss in addition to reduction in fat and lean mass exacerbates the risk for cachexia.

Infections such as HIV may alter metabolism, leading to weight loss.

Hormonal disruptions, such as an overactive thyroid (hyperthyroidism), may also exhibit as weight loss.

Recent research has shown fidgeting to result in significant weight loss.

Intentional weight loss refers to the loss of total body mass in an effort to improve fitness and health, and to change appearance.

Therapeutic weight loss, in individuals who are overweight or obese, can decrease the likelihood of developing diseases such as diabetes, heart disease, high blood pressure, stroke, osteoarthritis, and certain types of cancer.

Attention to diet in particular can be extremely beneficial in reducing the impact of diabetes and other health risks of an overweight or obese individual.

Weight loss occurs when an individual is in a state of negative energy balance: when the body is consuming more energy (i.e. in work and metabolism) than it is gaining (i.e. from food or other nutritional supplements), it will use stored reserves from fat or muscle, gradually leading to weight loss.