OBJECTIVES: To determine the epidemiology and clinical presentation of virus-associated acute respiratory infections (ARI) in Mozambican infants. METHODS: A systematic selection of nasopharyngeal aspirates (n = 333), collected from infants younger than 12 months who visited Manhica District Hospital (southern Mozambique) with ARI during a 12 months respiratory syncitial virus surveillance, were tested for other common respiratory viruses. Four different polymerase chain reactions were used to diagnose rhinovirus (RV), influenza (Flu; A and B), adenovirus (ADV), human metapneumovirus (hMPV), parainfluenza (PIV; 1, 2, 3 and 4AB) and enterovirus (EV). RESULTS: At least one study virus was identified in more than half of the samples tested (185/333). Overall, 231 viruses were detected among 185 infants, listed in the order of prevalence: RV (26%), Flu (15%), ADV (14%), hMPV (7%), PIV (5%) and EV (3%). Acute respiratory infections (ARI) cases and viral episodes were seasonal and concentrate during the warm and the rainy season. Clinical features were similar among all study children regardless of the detection of virus, with the exception of ear discharge, which was more frequent among viral cases [6% (11/183) vs. 1% (2/144); P = 0.034]. Children with multiple viral infections had higher odds of severity such as nasal flaring and indrawing (OR = 2.7, P = 0.028 and OR = 3.8, P = 0.007, respectively) and higher odds of hospitalisation (OR = 4.42, P = 0.001, adjusted by age and sex). CONCLUSIONS: Viral ARI are frequent among infants visited in MHD. Strategies to prevent mild respiratory infections, and specially their complications, might alleviate health systems of source-limited settings.