The epidural space is the vertical area between the dura mater and the vertebral wall; this contains fat, arteries, and a venous plexus. SEAs are most commonly located posteriorly, and in the thoracolumbar region (where the epidural space is larger). Abscesses that begin at one level often extend longitudinally; and may also extend locally into the paravertebral tissue or spinal musculature, giving rise to an iliopsoas abscess.

Staphylococcus aureus causes about two-thirds of cases. This is because most predisposing factors allow for invasion by skin flora. Some of these cases are due to methicillin-resistant S. aureus (MRSA); the incidence varies by setting. In order of frequency, the other pathogens encountered include Gram-negative bacilli, Streptococci, coagulase-negative Staphylococci; and rarely, anaerobes, fungi, parasites, and in resource-limited settings, Mycobacterium tuberculosis. Note that post-neurosurgical patients are more likely to have resistant Gram-negative organisms.