Background: Flares of systemic capillary leak syndrome (SCLS) release plasma into peripheral tissues, which typically leads to hypotensive shock and multiple organ dysfunction (1). Anasarca and compartment syndromes may develop as a result of excessive intravenous (IV) fluid administration (2). Between episodes, patients are typically asymptomatic. The diagnosis of SCLS is based on characteristic clinical findings that include hypotension, hemoconcentration, and hypoalbuminemia. Prophylaxis with IV immunoglobulin (IVIG) is disease sparing and improves survival (3).

We describe 3 patients who had severe flares of SCLS immediately after receiving standard doses of the COVID-19 vaccines that have emergency use authorization from the U.S. Food and Drug Administration. These events were classified as non–dose-related, unexpected, and serious adverse events according to the World Health Organization.

Objective: To alert clinicians to the possibility of SCLS-like events immediately after COVID-19 vaccination.