During the SARS-CoV-2 pandemic, the pediatric emergency department (ED) of Bologna, Emilia-Romagna, Italy faced a reorganization to better deal with the new clinical needs. We herein describe the main changes in the organization and in the attendances to our pediatric ED. From the 1 March 2020 to the 31 January 2022, 796 children positive for SARS-CoV-2 presented to our pediatric ED, but only 26 required hospitalizations, of which only 9 for COVID-19 related reasons. During this period, we also registered a temporal correlation between multisystem inflammatory syndrome in children (MIS-C) admissions and the peaks of SARS-CoV-2 infection in the Italian population. Respiratory syncytial virus (RSV) remained during last year the viral infection with the highest hospitalization rate. The analysis and description of the changes in the activity of the pediatric ED during the SARS-CoV-2 pandemic may help to better understand the routinary activity and be prepared for any possible new challenge.