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Background: Coronavirus disease 2019 (COVID‐19) is a global health emergency. Despite the widely hypothesized role of a cytokine storm in disease severity, no study thus far has explored the association between immunosuppression and disease severity in patients hospitalized with COVID‐19. Objective: This study aimed to examine the association between the use of immunosuppressant medication and outcomes of patients hospitalized with COVID‐19. Methods: Nine hundred and eighty‐one consecutive patients hospitalized between 12 March 2020 and 15 April 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), were enrolled in this cohort study and subdivided by immunosuppression status. The patients were followed up for a minimum of 28 days (median 37 days) for the primary end‐point of mortality. Secondary end‐points included the composite of intubation or death, and the composite of mortality, intubation or continuous positive airway pressure (CPAP) requirement. Results: During the follow‐up period, 354 (36.1%) of study patients died. The immunosuppressed cohort (n = 31) had significantly higher mortality rates (aHR: 2.067, 95% CI: 1.20–3.57, P = 0.009). There was no association between immunosuppression and the composite end‐point of mortality or intubation (aHR: 1.49 95% CI: 0.88–2.51, P = 0.14) and of the composite end‐point of mortality, intubation or CPAP (aHR: 1.36 95% CI: 0.81–2.30 P = 0.245). Conclusion: In this cohort study of 981 confirmed COVID‐19 patients consecutively hospitalized at a large North West London hospital, immunosuppressant use was associated with significantly higher mortality rates. These results support the current UK government's early isolation ('shielding') policy for these individuals and should be used to guide future research. [ABSTRACT FROM AUTHOR]