Background and Objectives. The intensive care unit (ICU), especially in an infectious disease hospital, is both an area with a high consumption of antibiotics (atb) and a “reservoir” of multidrug-resistant bacteria. We proposed the analysis of antibiotic therapy practices in such a department that treated, in conditions of a pandemic wave, patients with COVID-19 and its complications. Materials and Methods. This was a retrospective transversal study of 184 COVID-19 patients treated in the ICU of a regional infectious disease hospital of Iaşi, Romania, in a 3-month interval of 2020 and 2021. Results. All the included patients (Caucasians, 53% males, with a median age of 68 years, and a Charlton comorbidity index of 3) received at least one antibiotic during their stay in the ICU (43% also had antibiotics prior to hospital admission and 68% in the Infectious Diseases ward). Only 22.3% of the ICU patients had only one antibiotic. A total of 77.7% of them started with an association of two antibiotics, and 19.6% of them received more than three antibiotics. The most-used ones were linezolid (77.2%), imipenem (75.5%), and ceftriaxone (33.7%). The median atb duration was 9 days. No change in the number or type of atb prescription was seen in 2021 (compared to 2020). Only 9.8% of the patients had a microbiological confirmation of bacterial infection. A total of 38.3% of the tested patients had elevated procalcitonin levels at ICU admission. The overall fatality rate was 68.5%, with no significant differences between the two analyzed periods or the number of administered antibiotics. More than half (51.1%) of the patients developed oral candidiasis during their stay in the ICU, but only 5.4% had C. difficile colitis. Conclusion. Antibiotics were widely used in our ICU patients in the presence of a reduced microbiological confirmation of a bacterial co-infection, and were justified by other clinical or biological criteria.