Objective To study the association between adverse outcomes during hospitalization and early postnatal weight changes in term appropriate-for-gestational-age (AGA) infants with early-onset sepsis (EOS). Methods A retrospective study was conducted on clinical data of term AGA infants with EOS admitted to the Children's Hospital of Chongqing Medical University from January 2023 to September 2024. The infants were divided into a weight-gain group (weight difference > 0 kg; n=229) and a no-weight-gain group (weight difference ≤ 0 kg; n=131) based on the change in weight from birth to postnatal day 7, and the incidence of adverse outcomes during hospitalization was compared between groups. Results Length of hospital stay, duration of antibiotic use, and duration of mechanical ventilation in the weight-gain group were longer than those in the no-weight-gain group (P<0.05). The incidence of acute kidney injury, electrolyte imbalance, intracranial hemorrhage, patent ductus arteriosus, moderate-to-severe pulmonary arterial hypertension, and pulmonary hemorrhage was higher in the weight-gain group than in the no-weight-gain group (P<0.05). Daily net fluid balance on postnatal days 5 and 6, and cumulative net fluid balance on postnatal days 5-7, were higher in the weight-gain group than in the no-weight-gain group (P<0.05). Conclusions Early postnatal weight gain in term AGA infants with EOS is associated with an increased incidence of adverse outcomes during hospitalization, and weight change can serve as one of the indicators to assess neonatal fluid balance.