We explored viral and symptom rebound after coronavirus disease 2019 amubarvimab-romlusevimab monoclonal antibody therapy versus placebo in the randomized ACTIV-2/A5401 trial. Participants underwent nasal severe acute respiratory syndrome coronavirus 2 polymerase chain reaction testing at study days 3, 7, 14, and 28. Viral rebound was defined as RNA ≥3 and ≥0.5 log10 copies/mL increase from day 3 or 7, and symptom rebound as hospitalization or any moderate/severe symptom for ≥2 days after initial symptom improvement. There was no difference in viral rebound (∼5%/arm) (analysis population n = 713) or symptom rebound among participants who initially improved (hazard ratio, 0.95 [95% confidence interval, .52-1.75]; analysis population n = 574); <1% had both viral/symptom rebound.