The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to widespread use of hydroxychloroquine and azithromycin despite the lack of conclusive evidence for their safety and efficacy. We evaluated the association between treatment with hydroxychloroquine and/or azithromycin and hospital mortality as the primary outcome. We compared the hospital mortality of patients treated with hydroxychloroquine alone, azithromycin alone, or their combination to the mortality of patients who received neither drug. A logistic multivariate model with overlap weight propensity score was used for estimation of odds ratios (ORs) with 95% confidence intervals (95% CIs). One thousand four hundred and three patients with SARS-CoV-2 infection were admitted to the hospital. At the time of the analysis, the outcome was available for 1376 (98%) of them. Five hundred and eighty-seven patients (42%) received azithromycin and 377 patients (27%) received hydroxychloroquine, alone or in combination. In-hospital mortality was 26%. After the adjusted analysis, azithromycin alone was associated with lower mortality (OR 0.60, 95% CI 0.42-0.85) compared to no treatment. Hydroxychloroquine alone (OR 0.76, 95% CI 0.53-1.08) and the combination of azithromycin and hydroxychloroquine (OR 1.13, 95% CI 0.77-1.69) were not associated with hospital mortality. In this cohort of patients, azithromycin alone was associated with lower hospital mortality but hydroxychloroquine was not associated with increased or reduced mortality. While we await randomized clinical trials, these data support the use of azithromycin in novel coronavirus disease 2019 (COVID-19) and can contribute to better understanding of its role in further meta-analyses.