Introduction: During the COVID-19 pandemic, the frequency of antibiotic use has increased globally. The most serious consequence of the excessive use of antibiotics is the development of multiresistant pathogens, which requires long-term treatment with unpredictable outcomes and causes large costs within the health system. Objectives: The primary objective of the conducted research was to determine the frequency of use and type of antibiotic therapy for COVID-19 patients hospitalized in KBC Split. The secondary objective was to show the association of the use of antibiotic therapy with comorbidities, selected laboratory findings and death. Participants and procedures: The retrospective study is part of a larger multicenter study and was conducted on a cohort of 285 patients hospitalized at the Clinic for Infectious Diseases in Split during October and November 2020. For each participant, 244 items from discharge letters were searched, and the analysis included the following variables: age and gender, number of days spent in hospital treatment, data on previous illness, antibiotic therapy used, diagnosed pneumonia, systolic and diastolic blood pressure values, and laboratory findings: value of peripheral blood oxygen saturation, concentration of urea, creatinine, total bilirubin, D dimer and proportion of neutrophils and lymphocytes. Results: Data on the use of antibiotic therapy refer to 266 subjects. The majority of subjects were treated with antibiotics (N = 239 (84 %)). Patients on antibiotic therapy had more comorbidities compared to patients without antibiotic therapy (P = 0.008). The most common comorbidities included diseases of the cardiovascular system, but arterial pressure was the same in patients with and without antibiotic therapy. The antibiotic of choice was azithromycin in 141 (59%) patients. The second most frequently used antibiotic was amoxicillin with clavulanic acid, used in 117 (49%) patients. Ceftriaxone was used in 51 patients (21%), and only one patient was treated with doxycycline (0.4%). Multiple antibiotic therapy was used in 41% of patients. The concentration of urea, creatinine, total bilirubin and D-dimer did not differ between patients with regard to the use of antibiotic therapy. Conclusions: Patients on antibiotic therapy more often had hypoxemia and a greater number of comorbidities. Most often, they were treated with azithromycin, and antibiotic treatment was not associated with a fatal outcome. Antibiotic treatment of COVID-19 patients is not contraindicated, but requires individual clinical judgment for each patient and should be carried out in accordance with existing guidelines.