Whether pediatric rotavirus infection is associated with extra-intestinal complications remains unknown.We conducted a case-control study to investigate the incidences and risks of rotavirus-associated extra-intestinal complications in hospitalized newborns, infants and children younger than 5 years.A total of 1,325 young inpatients with rotavirus infection (754 male and 539 newborns) and 1,840 controls without rotavirus infection (1,035 male and 836 newborns) were included. The incidences of neurological disease were higher among rotavirus individuals compared with controls: newborns, 7.24% (39/539) vs 2.87% (24/836), p < 0.001; infants and young children, 19.59% (154/786) vs 12.35% (124/1,004), p < 0.001. The associated odd ratios (ORs; 95%CI) for neurological disease frequency following rotavirus infection was 2.64 (1.57-4.44) for newborns; and 1.73 (1.34-2.24) for infants and young children, which climbed to 2.56 (1.57-4.18) in Case-Control (1:1) Matching analysis and 1.85 (1.41-2.42) in confounder adjustment. Moreover, rotavirus infection was associated with other extra-intestinal complications, depending on study population and disease severity. Outcome analysis revealed that rotavirus infection and subsequent consequences had a significant impact on hospitalization and discharge in clinical practice.Rotavirus exposure was associated with a spectrum of extra-intestinal complications, particularly neurological disease. Rotavirus infection and subsequent consequences resulted in poor clinical outcomes.© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.