Abstract Background Increased prescribing of antibiotics commonly used for respiratory infections, including azithromycin, ceftriaxone, and doxycycline was observed in nursing homes (NH) during the COVID-19 pandemic however antibiotic prescribing was not linked to resident diagnosis. Therefore, our objective was to characterize antibiotic prescribing in residents with SARS-CoV-2 infection in a large cohort of US NHs. Methods We conducted a retrospective cohort study using PointClickCare (PCC) data containing longitudinal NH electronic health records. We included 4,891 NHs that reported ≥1 medication order/month from April 2020-November 2021. We identified the first onset of SARS-CoV-2 infection using ICD-10-CM diagnosis code U07.1. To validate the number of SARS-CoV-2 infections per facility captured in PCC, we compared the total number of SARS-CoV-2 infections documented in PCC to those reported to the National Healthcare Safety Network (NHSN). Antibiotic orders were determined to be associated with a SARS-CoV-2 infection if 3 days before or ≤7 days after diagnosis. We characterized the proportion of residents with a SARS-CoV-2 infection with an associated antibiotic by month. Results We included 2,086 (43%) NHs that had ≤20% difference in total number of SARS-CoV-2 infections documented in PCC and reported to NHSN. From April 2020-November 2021, a total of 118,180 residents with a SARS-CoV-2 infection were identified and 24% had an associated antibiotic prescription (N=27,972). The highest prescription rate (30%, 95% Confidence Interval [29%-31%]) was observed in April 2020 and varied by less than 8% from May 2020-November 2021 (Fig.1). The most commonly prescribed antibiotics were azithromycin (53%), doxycycline (13%) and ceftriaxone (10%). Conclusion An antibiotic prescription was linked to up to a quarter of NH residents with SARS-CoV-2 infection, highlighting potential opportunities for avoiding unnecessary antibiotic prescribing for viral infections in NHs. Appropriate antibiotic prescribing in NH populations is important to reduce potential harm when antibiotics offer no treatment benefit to the resident. Identifying facility-level characteristics that lead to variability in antibiotic prescribing is a next step to inform antibiotic stewardship interventions. Disclosures All Authors: No reported disclosures.