Objective: To examine the association between antidepressant use and the risk of intubation or death in hospitalized patients with COVID-19. Design: Multicenter observational retrospective cohort study. Setting: Greater Paris University hospitals, France. Participants: 7,345 adults hospitalized with COVID-19 between 24 January and 1 April 2020, including 460 patients (6.3%) who received an antidepressant during the visit. Data source: Assistance Publique-Hopitaux de Paris Health Data Warehouse. Main outcome measures: The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusting for patient characteristics (such as age, sex, and comorbidities), disease severity and other psychotropic medications. The primary analyses were multivariable Cox models with inverse probability weighting. Results: Over a mean follow-up of 18.5 days (SD=27.1), 1,331 patients (18.1%) had a primary end-point event. Unadjusted hazard ratio estimates of the association between antidepressant use and the primary outcome stratified by age (i.e., 18-50, 51-70, 71-80, and 81+) were non-significant (all p>0.072), except in the group of patients aged 71-80 years (HR, 0.66; 95% CI, 0.45 to 0.98; p=0.041). Following adjustments, the primary analyses showed a significant association between use of any antidepressant (HR, 0.64; 95% CI, 0.51 to 0.80; p<0.001), SSRI (HR, 0.56; 95% CI, 0.42 to 0.75; p<0.001), and SNRI (HR, 0.57; 95% CI, 0.34 to 0.96; p=0.034), and reduced risk of intubation or death. Specifically, exposures to escitalopram, fluoxetine, and venlafaxine were significantly associated with lower risk of intubation or death (all p<0.05). These associations remain significant in multiple sensitivity analyses, except for the association between SNRI use and the outcome. Conclusions: SSRI use could be associated with lower risk of death or intubation in hospitalized patients with COVID-19. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.