Molecular assays have resulted in increased detection of viral respiratory infections, including virus coinfection, from children with acute respiratory infections. Yet the clinical severity of virus coinfection compared to single virus infection remains uncertain. We performed a retrospective study of children presenting with acute respiratory infections comparing clinical severity of single respiratory virus infection to virus coinfection, detected on midturbinate swabs by molecular assays. Patient characteristics and measures of clinical severity were abstracted from health records. A total of 472 virus-infected children were included, 391 with a single virus infection and 81 with virus coinfection. Virus status did not affect admission to hospital (odds ratio (OR) = 0.8; 95 % confidence interval (CI) 0.5-1.4; p 0.491) or clinical disease severity among inpatients (OR = 0.8; 95% CI 0.5-1.5; p 0.515) after adjusting for age and underlying comorbidities. However, children infected with rhinovirus/enterovirus (HRV/ENT) alone were more likely to be admitted to the hospital compared to those coinfected with HRV/ENT and at least another virus, although this was not significant in multivariable analyses (OR 0.47; 95% CI 0.22-1.0; p 0.051). In multivariable analyses, children coinfected with respiratory syncytial virus (RSV) and other viruses were significantly more likely to present with radiologically confirmed pneumonia compared to those with an isolated RSV infection (OR 3.16, 95% CI 1.07-9.34, p 0.037). Equivalent clinical severity was observed between children with single virus infection and virus coinfection, although children coinfected with RSV and other viruses presented more frequently with pneumonia than those with single RSV infection. Increased disease severity observed among children with single HRV/ENT infection requires further investigation.