To investigate potential respiratory pathogens in children with community-acquired pneumonia (CAP) and risk factors for severe disease. This prospective study was conducted among 467 children at the Thai Binh Paediatric Hospital, Vietnam between 1 July 2020 and 30 June 2021. Clinical data and laboratory results were collected. Twenty-four respiratory microorganisms were tested from nasopharyngeal swabs using real-time PCR. Logistical regression was used to estimate a factor's adjusted odd ratios of the severity of disease. Mean age of patients = 15.4 ± 13.3 months, 63.0% were male. Over 97% of patients had a positive PCR result. 87% of patients were positive for multiple (up to eight) microorganisms. Rhinovirus (46%), respiratory syncytial virus (RSV) (24%), enterovirus (17%), and parainfluenza viruses-3 (13%) were the most frequent viruses. H. influenzae (61%), S. pneumoniae (45%) and M. catarrhalis (30%) were the most common bacteria. 128 (27%) cases were classified as severe pneumonia. Presence of smokers at home (aOR 2.11, 95% CI 1.27-3.52, P value = 0.004), CRP level ≥ 50 mg/dL (aOR  6.11, 95% CI  3.86-9.68, P value < 0.0001), RSV (aOR  1.78, 95% CI  1.07-2.96, P value = 0.03) and H. influenzae (aOR  1.66, 95% CI  1.03-2.67, P value = 0.04) PCR detection associated with a higher risk of severe pneumonia; ,. Causative agents of pneumonia in children are complex. Children positive with RSV and H. influenzae need to be closely monitored to prevent severe pneumonia.