Abstract Objectives To evaluate whether subcutaneous neutralizing monoclonal antibody (mAb) treatment given in the emergency department (ED) setting was associated with reduced hospitalizations, mortality, and severity of disease when compared to nontreatment among mAb‐eligible patients with coronavirus disease 2019 (COVID‐19). Methods This retrospective observational cohort study of ED patients utilized a propensity score‐matched analysis to compare patients who received subcutaneous casirivimab and imdevimab mAb to nontreated COVID‐19 control patients in November–December 2021. The primary outcome was all‐cause hospitalization within 28 days, and secondary outcomes were 90‐day hospitalization, 28‐ and 90‐day mortality, and ED length of stay (LOS). Results Of 1340 patients included in the analysis, 490 received subcutaneous casirivimab and imdevimab, and 850 did not received them. There was no difference observed for 28‐day hospitalization (8.4% vs. 10.6%; adjusted odds ratio [aOR] 0.79, 95% confidence intervals [CI] 0.53–1.17) or 90‐day hospitalization (11.6% vs. 12.5%; aOR 0.93, 95% CI 0.65–1.31). However, mortality at both the 28‐day and 90‐day timepoints was substantially lower in the treated group (28‐day 0.6% vs. 3.1%; aOR 0.18, 95% CI 0.08–0.41; 90‐day 0.6% vs. 3.9%; aOR 0.14, 95% CI 0.06–0.36). Among hospitalized patients, treated patients had shorter hospital LOS (5.7 vs. 11.4 days; adjusted rate ratio [aRR] 0.47, 95% CI 0.33–0.69), shorter intensive care unit LOS (3.8 vs. 10.2 days; aRR 0.22, 95% CI 0.14–0.35), and the severity of hospitalization was lower (aOR 0.45, 95% CI 0.21–0.97) compared to untreated. Conclusions Among ED patients who presented for symptomatic COVID‐19 during the Delta variant phase, ED subcutaneous casirivimab/imdevimab treatment was not associated with a decrease in hospitalizations. However, treatment was associated with lower mortality at 28 and 90 days, hospital LOS, and overall severity of illness.