Although much of the response to the SARS-CoV-2 pandemic has focused on acute COVID-19 illness, accumulating evidence demonstrates morbidity beyond acute SARS-CoV-2 infection. At least 2 other periods of illness appear to be temporally associated with SARS-CoV-2 infection: a rare post-acute hyperinflammatory illness and late inflammatory and virological sequelae. These 3 illness periods not only define the temporal course of SARS-CoV-2 infection at the population level but also capture distinct phases of host-viral interaction. A theoretical framework describing illness periods of SARS-CoV-2 infection (including clinical presentations and timing of onset), their pathophysiological underpinnings, and associated key laboratory findings may contribute to a more inclusive and ordered understanding of the natural history of SARS-CoV-2 infection and enhance research efforts. Within the proposed framework, a patient may experience any combination of these illnesses or may have asymptomatic infection without illness.