The work consists of twenty-three devotions, each in three parts--a meditation, an expostulation, and a prayer--recording and exploring Donne’s experience of illness (probably typhus). The work traces the disease’s course and treatment, beginning in the first devotion with the first signs of illness, moving through the patient’s taking to bed and sending for physicians, their prescribing and carrying out various treatments, and a worsening of symptoms followed by the crisis where, in Devotion 17, the patient prepares himself for death. He then begins to recover, the physicians purge him, and, like Lazarus, he rises from his bed. The physicians then try to correct the cause of the disease in him, and, in the final devotion, warn the patient that a relapse is not out of the question.

Donne explores the spiritual implications of each stage of his illness, using the experience of his body to provoke reflections on the health of the soul. For instance, in the first devotion he asks why sin, unlike physical sickness, does not show early signs which might enable one to get treatment in time. Donne uses the arrival of the physicians to explore Christ’s role as physician to the soul, and the spots which appear on his body to meditate on Christ as the unspotted carrier of human stains.

Anticipating death, he considers the relationship of soul and body, seeing the body’s death as the cure of the disease. He then sees the physicians as God’s instruments in curing his body and miraculously raising him from illness. Finally, he argues that the root of all illness is internal, lying in the sin which infects his soul, and that therefore he must work constantly to prevent the relapse which continues to threaten.