Objective: To identify the differential diagnoses of severe COVID-19 and the distinguishing characteristics of critically ill COVID-19 patients in Reunion Island to help improve the triage and management of patients in this tropical setting. Methods: This retrospective observational study was conducted from 11 March to 4 May 2020 in the only intensive care unit (ICU) authorised to manage COVID-19 patients in Reunion Island, a French overseas department located in the Indian Ocean region. All patients with unknown COVID-19 status were tested by polymerase chain reaction (PCR) on ICU admission; those who tested negative were transferred to the COVID-19-free area of the ICU. Results: Over the study period, 99 patients were admitted to our ICU. A total of 33 patients were hospitalised in the COVID-19 isolation ward, of whom 11 were positive for COVID-19. The main differential diagnoses of severe COVID-19 were as follows: community-acquired pneumonia, dengue, leptospirosis causing intra-alveolar haemorrhage and cardiogenic pulmonary oedema. The median age of COVID-19-positive patients was higher than that of COVID-19-negative patients (71 [58–74] vs. 54 [46–63.5] years, P = 0.045). No distinguishing clinical, biological or radiological characteristics were found between the two groups of patients. All COVID-19-positive patients had recently travelled or been in contact with a recent traveller. Conclusions: In Reunion Island, dengue and leptospirosis are key differential diagnoses of severe COVID-19, and travel is the only distinguishing characteristic of COVID-19-positive patients. Our findings apply only to the particular context of Reunion Island at this time of the epidemic. © 2020 John Wiley & Sons Ltd