Staphylococcus aureus is a relevant pathogen in bloodstream infections (BSI), and the emergency of the COVID-19 pandemic increased its antimicrobial resistance. S. aureus isolates from BSI (September/2019 - March/2021) were analyzed phenotypically and molecularly, in addition to the clinical features of the patients. Of 88 S. aureus isolates recovered from 85 patients, 25 were isolated before the pandemic and 63 during it, and 16 were from patients with COVID-19. A rate of 45.5% of methicillin-resistant isolates (MRSA) were found, and 5% of them were ceftaroline susceptible dose-dependent. Daptomycin non-susceptibility was observed in 9.1% of isolates. The USA800/ST5/SCCmecIV lineage was prevalent among MRSA isolates (41.8%). Besides, 30.2% of the isolates were associated with community-associated MRSA (CA-MRSA) genotypes. There was a significant impact on the resistance rates for cefoxitin, clindamycin and erythromycin among S. aureus isolates from BSI in COVID-19 patients and association with the previous use of azithromycin by them (p <
0.05). A clonal alternation and an increase in the emergence of CA-MRSA lineages were also found, highlighting the importance of constant microbiological surveillance.