Weight loss, in the context of medicine or health or physical fitness, is a reduction of the total body weight, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue.

A significant loss of total body weight is a serious, chronic illness. Substantial, unintentional weight loss is a symptom of acute or chronic illness, especially if other evidence is present.

Weight loss, for example, accompanied by insatiable thirst and hunger and fatigue may indicate diabetes mellitus, a chronic disease characterized by an abnormal accumulation of carbohydrates in the bloodstream due to insufficient production of insulin, a hormone produced in the pancreas that, when secreted into the bloodstream, permits cellular metabolism and utilization of glucose.

Poor management of insulin-dependent diabetes mellitus (IDDM), also known as diabetes mellitus type I, leads to an excessive amount of glucose and an insufficient amount of insulin in the bloodstream. This triggers the release of triglycerides from adipose tissue and catabolism of amino acids in muscle tissue. This results in a loss of both fat and lean mass, predisposing a significant reduction in total body weight.

A myriad of additional scientific considerations are applicable to weight loss, including but not limited to physiological and exercise sciences, nutrition science, behavioral sciences, and other sciences.

One area involves the science of bioenergetics including biochemical and physiological energy production and utilization systems, that is frequently evidence of diabetes, and ketone bodies, acetone particles occurring in body fluids and tissues involved in acidosis, also known as ketosis, somewhat common in severe diabetes.

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. And fluid loss in addition to a 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.