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Abstract This retrospective cohort study conducted in Turkey between December 2020 and June 2022 aimed to assess antibiotic use, bacterial co-infections, and the associated factors on mortality in hospitalized patients with mild-to-severe COVID-19. Among the 445 patients, 80% received antibiotics, with fluoroquinolones being the most common choice, followed by beta-lactams and combinations. Various clinical and laboratory parameters, including symptoms, comorbidities, CCI, oxygen requirements, and CRP levels were observed to be elevated in the antibiotic group. Non-survivors had more ICU admissions and longer hospital stays compared to survivors. We conducted a multivariate Cox regression analysis to evaluate factors related to mortality. However, we did not find an association between antibiotic use and mortality [HR 2.7 (95% CI 0.4–20)]. The study identified significant factors associated with an antibiotic prescription, such as CCI (OR 1.6), CRP (OR 2.3), and ICU admission (OR 8.8), (p |