Lymphatic fluid is normally transported out of a region of the body by an extensive network of lymph vessels. When the collection of protein-rich fluid persists in a specific area, it can attract more fluid and thus worsen the swelling. In addition to increased fluid in the area, the body experiences an inflammatory reaction resulting in scar tissue called fibrosis in the affected area. The presence of fibrosis makes it even more difficult for the excess fluid to be eliminated from the area. As a result, the increased fluid and fibrosis prevents the delivery of oxygen and essential nutrients to the area, which in turn can delay wound healing, provide a culture medium for bacteria to grow, and increase the risk of infections in or below the skin called cellulitis or lymphangitis (discussed later under Infections and Other Complications).

Lymphedema should not be confused with other types of edema resulting from venous insufficiency (leaky or obstructed veins), cardiac conditions like heart failure or sleep apnea, kidney failure, or other inflammatory processes. These conditions are not lymphedema and are generally treated differently.