The most common causes of muscle pain and spasm are musculoskeletal injuries and a nutritional deficiency. These broad categories of causes, however, have "sub-causes." Injuries and nutritional deficiencies can be caused by playing sports, an accident, loss of blood flow to the muscle, infection or the presence of a tumor. Muscle pain and spasm can have more than one cause, so the common and the not-so-common causes should be carefully considered to arrive at a correct diagnosis. The severity and type of discomfort that sufferers of muscle pain and spasm are experiencing — such as mild or severe, local or diffuse — also should be considered.

Musculoskeletal injuries, particularly a fractured femur or thigh bone, almost always cause severe muscle pain and spasm. This results from the sometimes violent contraction of muscles which in turn causes the movement of jagged ends of bone cutting and "stabbing" surrounding soft tissue. Splinting is performed not only to greatly reduce blood loss, but also to stop the muscle pain and spasm that can accompany the injury.

Low levels of calcium appears on the list of nutritional deficiencies that could lead to a person of any age experiencing muscle pain and spasm. What many people do not realize about nutritional deficiencies is that low levels of a nutrient are not automatically raised by increasing intake of that nutrient. Muscle pain and spasm caused by low levels of calcium might have been brought on by low levels of vitamin D, because sufficient vitamin D is required for proper absorption of calcium. A deficiency of the mineral magnesium can also be the underlying cause of muscle pain and spasm.

Some people believe that aging should be considered a common cause for any kind of problem, disorder or disease of the musculoskeletal system. Although it is true that the mature population tends to experience health problems of this and every other type, muscle pain and spasm do not occur in many mature people. This fact causes some people to reject aging as a common cause. It also should be remembered that what is a common cause in one person is not necessarily a common cause in another. For example, people who play sports, suffer from an autoimmune disease, have any kind of infection or tumor or have any other condition that restricts blood flow to the muscle could consider their lifestyle and state of health to be the "cause" of the discomfort.