Objective: Systemic capillary leak syndrome (SCLS) is a severe condition characterized by the coexistence of hypovolaemic shock, haemococentration, and hypoalbuminaemia, without albuminuria, that may progress to multiorgan failure and an unfavourable outcome. Its development is often triggered by viral infections, such as influenza A virus, but it is unclear whether it is also triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We aimed to investigated the association between SARS-CoV-2 and SCLS.Method: We present the case of a 55-year-old-woman affected by SARS-CoV-2 infection who developed SCLS. Moreover, we performed a systematic review of the literature to identify any common features with other cases and to describe clinical characteristics and outcomes.Results: We found three other cases of SCLS occurring during SARS-CoV-2 infection in 2020. Taking all cases together, the mean age was 50 years (range 38-63), with a 1:1 gender ratio. Respiratory manifestations were the most common symptom, and all patients required admission to the intensive care unit. The mortality rate was 50%.Conclusions: SARS-CoV-2 infection may trigger SCLS disease, either by an overproduction of proinflammatory cytokines or by direct viral infection of the endothelium. Since SCLS may have a poor prognosis, in every SARS-CoV-2-infected patient presenting the suggestive triad of hypovolaemic shock, haemoconcentration, and hypoproteinaemia, an SCLS diagnosis should be considered and early treatment initiated.