Objectives To compare the epidemiological, clinical profile, intensive care needs and outcome of children hospitalized with SARS-CoV-2 infection during the first and second waves of the pandemic. Methods This was a retrospective study of all children between 1 mo and 14 y, admitted to a dedicated COVID-19 hospital (DCH) during the first (1st June to 31st December 2020) and second waves (1st March to 30th June 2021). Results Of 217 children, 104 (48%) and 113 (52%) were admitted during the first and second waves respectively. One hundred fifty-two (70%) had incidentally detected SARS-CoV-2 infection, while 65 (30%) had symptomatic COVID-19. Comorbidities were noted in 137 (63%) children. Fifty-nine (27%) and 66 (30%) children required high-dependency unit (HDU) and ICU care respectively. Severity of infection and ICU needs were similar during both waves. High-flow oxygen ( n = 5, 2%), noninvasive ventilation [CPAP ( n = 34, 16%) and BiPAP ( n = 8, 5%)] and invasive ventilation ( n = 45, 21%) were respiratory support therapies needed. NIV use was more during the second wave (26% vs. 13%; p = 0.02). The median (IQR) length (days) of DCH stay among survivors was longer during the first wave [8 (6–10) vs. 5.5 (3–8); p = 0.0001]. Conclusions Disease severity, associated comorbidities, PICU and organ support need and mortality were similar in the first and second waves of the pandemic. Children admitted during the second wave were younger, had higher proportion of NIV use and shorter length of COVID-19 hospital stay. Supplementary Information The online version contains supplementary material available at 10.1007/s12098-022-04283-0.