A large study investigating the aetiologies of acute febrile illness (AFI) in hospitalized patients demonstrated important and novel findings. In a cohort of 976 children and adults hospitalized in southern Sri Lanka, viruses were the predominant cause of infection, accounting for over 50% of cases. Dengue was the most common specific cause, followed by respiratory viruses such as influenza A, influenza B, parainfluenza virus, HRV/HEV, RSV, and seasonal coronaviruses. Bacterial infections such as leptospirosis, rickettsial infections, scrub typhus, and Q fever comprised a smaller but important part of the cohort. By employing comprehensive molecular and serologic testing, we were able to identify an etiology of infection in over two-thirds of the cohort. Furthermore, we observed a trend of excessive prescribing of antibiotics for viral infections ( 45.5% of patients with viral infections received antibiotics at enrolment into the study) and inadequate use for bacterial ones (only 62.3% of patients with bacterial infections received antibiotics at enrolment).