INTRODUCTION: In the absence of a universally accepted association between smoking and COVID-19 health outcomes, we investigated this relationship in a representative cohort from one of the world's highest tobacco consuming regions. This is the first report from the Middle East and North Africa that tackles specifically the association of smoking and COVID-19 mortality while demonstrating a novel sex-discrepancy in the survival rates among patients. METHODS: Clinical data for 743 hospitalized COVID-19 patients was retrospectively collected from the leading centre for COVID-19 testing and treatment in Lebanon. Logistic regression, Kaplan-Meier survival curves and Cox proportional hazards model adjusted for age and stratified by sex were used to assess the association between the current cigarette smoking status of patients and COVID-19 outcomes. RESULTS: In addition to the high smoking prevalence among our hospitalized COVID-19 patients (42.3%), enrolled smokers tended to have higher reported ICU admissions (28.3% vs 16.6%, p<0.001), longer length of stay in the hospital (12.0 +/- 7.8 vs 10.8 days, p<0.001) and higher death incidences as compared to non-smokers (60.5% vs 39.5%, p<0.001). Smokers had an elevated odds ratio for death (OR = 2.3, p<0.001) and for ICU admission (OR = 2.0, p<0.001) which remained significant in a multivariate regression model. Once adjusted for age and stratified by sex, our data revealed that current smoking status reduces survival rate in male patients ([HR] = 1.9 [95% (CI), 1.029-3.616]; p = 0.041) but it does not affect survival outcomes among hospitalized female patients([HR] = 0.79 [95% CI = 0.374-1.689]; p = 0.551). CONCLUSION: A high smoking prevalence was detected in our hospitalized COVID-19 cohort combined with worse prognosis and higher mortality rate in smoking patients. Our study was the first to highlight potential sex-specific consequences for smoking on COVID-19 outcomes that might further explain the higher vulnerability to death from this disease among men.