Antibiotics are frequently prescribed to patients with COVID-19. The aim was to determine the pattern of use of systemic antibiotics in a group of patients diagnosed with COVID-19 in Colombia between 2020–2022. This was a descriptive cross-sectional study designed to identify antibiotics prescription patterns for patients diagnosed with COVID-19 treated in eight clinics in Colombia. The AWaRe tool of the World Health Organization (WHO) was used to classify the antibiotics. A total of 10,916 patients were included. The median age was 57 years, and 56.4% were male. A total of 57.5% received antibiotics, especially ampicillin/sulbactam (58.8%) and clarithromycin (47.9%). Most of the antibiotics were classified as Watch (65.1%), followed by Access (32.6%) and Reserve (2.4%). Men (OR: 1.29; 95%CI: 1.17–1.43), older adults (OR: 1.67; 95%CI: 1.48–1.88), patients with dyspnea (OR: 1.26; 95%CI: 1.13–1.41), rheumatoid arthritis (OR: 1.94; 95%CI: 1.17–3.20), and high blood pressure at admission (OR: 1.45; 95%CI: 1.29–1.63), patients treated in-hospital (OR: 5.15; 95%CI: 4.59–5.77), patients admitted to the ICU (OR: 10.48; 95%CI: 8.82–12.45), patients treated with systemic glucocorticoids (OR: 3.60; 95%CI: 3.21–4.03) and vasopressors (OR: 2.10; 95%CI: 1.60–2.75), and patients who received invasive mechanical ventilation (OR: 2.37; 95%CI: 1.82–3.09) were more likely to receive a systemic antibiotic. Most of the patients diagnosed with COVID-19 received antibiotics, despite evidence showing that bacterial coinfection is rare. Antibiotics from the Watch group predominated, a practice that goes against WHO recommendations.