Ehrlichiosis is caused by Ehrlichia organisms, specifically E. chaffeensis, which causes human monocytic ehrlichiosis, or E. ewingii. These tiny gram-negative organisms multiply within white blood cell (WBC) cytoplasm. Clusters multiply to form large mulberry-shaped aggregates called morulae. Known vectors include the lone star tick (Amblyomma americanum), the American dog tick (Dermacentor variabilis), and the deer tick (Ixodes dammini and Ixodes scapularis).

Ehrlichiosis occurs worldwide, with prevalence related to the distribution of tick vectors. In the United States, most cases of ehrlichiosis are reported in the south-central and southern Atlantic areas of the country, but it has also been reported in the upper Midwest. Persons at highest risk include those who live in endemic and highly wooded areas, engage in activities in high grassy areas, and own a pet that may introduce a tick into the home. Because ehrlichiosis is not reportable to the health department, the exact incidence is unknown; however the CDC notes that reports of cases have increased from about 100 per year in 1999 to 600 per year in 2006.

It is unknown whether re-infection can occur or if infection confers immunity. More studies are being done to investigate this topic.

Complications of ehrlichiosis can be severe, especially if it is left untreated or occurs in immunocompromised patients. It can produce such complications as acute respiratory distress syndrome, disseminated intravascular coagulation (DIC), seizures, and coma. An estimated 1% to 5% of patients die as a result of the infection.