As according to Stokes' law the sedimentation velocity varies like the square of the object's diameter, larger aggregates settle faster.

The ESR is increased in inflammation, pregnancy, anemia, autoimmune disorders (such as rheumatoid arthritis and lupus), infections, some kidney diseases and some cancers (such as lymphoma and multiple myeloma).

The ESR is decreased in polycythemia, hyperviscosity, sickle cell anemia, leukemia, chronic fatigue syndrome,[4] low plasma protein (due to liver or kidney disease) and congestive heart failure.

[7] There are three stages in erythrocyte sedimentation:[8] In normal conditions, the red blood cells are negatively charged and therefore repel each other rather than stacking.

Non-inflammatory conditions that can cause raised ESR include anemia, kidney failure, obesity, ageing, and female sex.

Hemoglobinopathy such as sickle-cell disease can have low ESR due to an improper shape of red blood cells that impairs stacking.

In markedly increased ESR of over 100 mm/h, infection is the most common cause (33% of cases in an American study), followed by cancer (17%), kidney disease (17%) and noninfectious inflammatory disorders (14%).

[citation needed] The clinical usefulness of ESR is limited to monitoring the response to therapy in certain inflammatory diseases such as temporal arteritis, polymyalgia rheumatica and rheumatoid arthritis.

Additionally, ESR levels are used to define one of the several possible adverse prognostic factors in the staging of Hodgkin's lymphoma.

[7] Cases with raised CRP but normal ESR may demonstrate a combination of infection and some other tissue damage such as myocardial infarction, and venous thromboembolism.

However, in cases of low grade bacterial infections of bone and joints such as coagulase negative staphylococcus (CoNS), and systemic lupus erythematosus (SLE), ESR can be a good marker for the inflammatory process.

[31] According to a study released in 2015, a stop gain mutation in HBB gene (p. Gln40stop) was shown to be associated with ESR values in Sardinian population.

The red blood cell count, whose values are inversely related to ESR, is affected in carriers of this SNP.