Plasma and serum are both found in blood. Blood contains the red blood cells (RBC), the platelets, the white blood cells (WBC), and several other important substances such as electrolytes, fibrinogen, hormones, and antibodies, among many others. These are all suspended in the fluid portion of the blood, which is the plasma. The main difference between plasma and serum is the absence of fibrinogen, an important clotting factor, in the serum.

Both plasma and serum are without the RBC, WBC and platelets, but they contain all the other substances, except for the fibrinogen, which is not present in the serum. Inside the body, these blood components cannot be distinguished from each other, but in the laboratory, they can be separated and measured in order to help with the diagnosis and monitoring of diseases. An adequate amount of blood is usually extracted from the vein in the arm of the patient and placed in a clear test tube with the name of the patient on it. It is often accompanied by a list of laboratory tests to be done.

Certain tests may require the use of plasma and serum for the measurement of substances contained in blood. There are also tests that require only serum, such as the test for calcium, glucose, potassium, and cholesterol. When the laboratory tests to be done require the use of serum, the blood in the test tube is frequently spun in a centrifuge, a machine used to separate blood components. After spinning, a blood clot that contain the fibrinogen is often visible at the bottom of the tube, and the clear yellow liquid on top is the serum. The serum will then be separated from the clot, and be subjected to different test procedures.

When blood is exposed outside the body, its tendency is to clot due to the presence of the fibrinogen. Certain tests, such as the platelet function tests, often require the use of plasma. In order to separate the plasma from the solid components in blood and at the same time prevent it from clotting, an anticoagulant is usually added to the blood before spinning. Anticoagulants are chemicals that help prevent blood clot formation. They are also used as medications to prevent blood from clotting inside the bloodstream.

The transparency and color of plasma and serum are usually clear and yellowish. They can, however, become cloudy due to the presence of fats or to bacterial contamination. Plasma and serum may also appear reddish pink, which is a sign of hemolysis or breakdown of RBC. This usually occurs during blood extraction or from improper handling of the blood specimen. For these variations in the color of the plasma and serum, the blood sample may sometimes be rejected because it can cause inaccurate test results.