Résumé : Given the current scarcity of curative treatment of COVID-19, the search for an effective treatment modality among all available medications has become a priority. This study aimed at investigating the role of functional inhibitors of acid sphingomyelinase (FIASMAs) on in-hospital COVID-19 mortality. In this retrospective cohort study, we included adult in-patients with laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged hospital or deceased) from Erasme Hospital (Brussels, Belgium). We used univariate and multi-variate logistic regression models to explore the risk factors associated with in-hospital mortality. We included 350 patients (205 males, 145 females) with a mean age of 63.24 years (SD = 17.4, range: 21–96 years). Seventy-two patients died in the hospital and 278 were discharged. The four most com-mon comorbidities were hypertension (184, 52.6%), chronic cardiac disease (110, 31.4%), obesity (96, 27.8%) and diabetes (95, 27.1%). Ninety-three participants (26.6%) received a long-term prescription for FIASMAs. Among these, 60 (64.5%) received amlodipine. For FIASMAs status, multivariable regression showed increasing odds ratio (OR) for in-hospital deaths associated with older age (OR 1.05, 95% CI: 1.02–1.07; p = 0.00015), and higher prevalence of malignant neoplasm (OR 2.09, 95% CI: 1.03–4.22; p = 0.039). Nonsignificant decreasing OR (0.53, 95% CI: 0.27–1.04; p = 0.064) was reported for FIASMA status. For amlodipine status, multivariable regression revealed increasing OR of in-hospital deaths associated with older age (OR 1.04, 95% CI: 1.02–1.07; p = 0.0009), higher prevalence of hypertension (OR 2.78, 95% CI: 1.33–5.79; p = 0.0062) and higher prevalence of malignant neoplasm (OR 2.71, 95% CI: 1.23–5.97; p = 0.013), then secondarily decreasing OR of in-hospital death associated with long-term treatment with amlodipine (OR 0.24, 95% CI: 0.09–0.62; p = 0.0031). Chronic treatment with amlodipine could be significantly associated with low mortality of COVID-19 in-patients.