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Background: The Coronavirus disease 2019 (COVID-19) pandemic emerged in December 2019 and spread rapidly worldwide. So far, evidence regarding the breastfeeding and rooming-in management of mothers with COVID-19 and their newborn infants is scarce. Research Aims: 1) To assess the rate of exclusive breastfeeding at discharge among mothers with COVID-19 and their newborn infants managed either using a rooming-in or a separation regimen; and 2) to evaluate different neonatal outcomes, including the need for re-hospitalization related to COVID-19 among newborn infants in the two groups. Method: We conducted a retrospective two-group comparative observational study. The sample was participants with COVID-19 and their newborn infants ( N = 155 dyads) between March 1, 2020, and April 30, 2021. Two time periods were outlined resulting from the two different clinical practices of mother–infant separation and rooming-in. Results: Within the sample, 145 (93.5%) were asymptomatic. All neonates had documented Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test results, and six tested positive by reverse transcriptase polymerase chain reaction within 48 hr of life. The rate of exclusive breastfeeding was significantly higher ( p < .0001) within the rooming-in group. Length of hospital stay was significantly lower ( p = .001) within the rooming-in group. Conclusions: Protected rooming-in practice has proven to be safe and effective in supporting breastfeeding: None of the infants enrolled were hospitalized due to COVID-19 infection and the rate of exclusive breastfeeding at discharge was increased compared to those infants separated from their mothers.