Background <p>This study investigated the differences in clinical features of acute lower respiratory tract infection in children caused by suspected Omicron, respiratory syncytial virus (RSV), and influenza virus A (Flu A).</p> Methods <p>A retrospective analysis was conducted on the clinical data of 241 hospitalized children with lower respiratory tract infections due to suspected Omicron, RSV, or Flu A at Chengdu Women and Children’s Central Hospital from December 9, 2022 to August 1, 2023. Differences in age, sex, clinical characteristics, laboratory results, imaging findings, and fractional exhaled nitric oxide (FENO) results between the three viral infections were analyzed.</p> Results <p>Patients infected with suspected Omicron were predominantly infants and toddlers; in contrast, those infected with Flu A were mostly preschool children. Fever was most common in Flu A-infected patients, followed by RSV-infected and Omicron-infected patients. Inspiratory crackles in the lungs were most frequently observed in suspected Omicron-infected patients, whereas wheezing was more common in RSV-infected patients. No wheezing was observed in the lungs of any suspected Omicron-infected patients. Patients with both suspected Omicron and RSV infections had longer hospital stays. Notably, Flu A infection significantly decreased white blood cell count and increased neutrophil percentage (Neu%) compared with the other two infections. Furthermore, patients with suspected Omicron infection exhibited a pronounced reduction in Neu%; however, the decrease in lymphocyte percentage (Lym%) was considerable in all groups, with the Flu A-infected group showing the greatest decline. C-reactive protein levels were markedly higher in the RSV- and Flu A-infected groups. Liver function was significantly affected in suspected Omicron-infected patients, who were also more likely to have Mycoplasma pneumoniae or bacterial infections. Pulmonary consolidation was more common in suspected Omicron-infected patients, and they had the highest positive rate of FENO.</p> Conclusions <p>The clinical manifestations of suspected Omicron infection in patients with acute lower respiratory tract infections are similar to those of Flu A and RSV infections. However, these infections exhibit more severe liver function damage, lung consolidation, and airway inflammation. Paying attention to respiratory tract infections caused by the suspected Omicron virus in children is imperative to ensure timely and appropriate diagnosis and treatment. Promoting child vaccination remains crucial for safeguarding susceptible populations and protecting children’s health.</p>