Influenza is a malady related to the human respiratory system, and its influenza-like illness (ILI) can cause an economic and social burden, especially among children and the elderly. This study was conducted to estimate the cost of illness based on a social perspective of ILI cases. A prospective study was conducted between February and March of 2016 in pharmacies, private clinics at Khanh Hoa, Lam Dong, Tay Ninh, Dong Nai Province, and Ho Chi Minh City, and Hospital of Tropical Diseases. Demographic and clinical information were collected by face-to-face interview. Direct costs (e.g., diagnosis and therapeutics) and indirect costs (e.g., cost of day loss) are included as treatment costs. The average cost of treatment associated with ILI was US$ 88.09 per case for all age groups; direct non-medical cost was higher compared to direct medical cost: 39.5% in pharmacies, 71.1% in clinics, and 64.2% in hospital. The indirect cost was US$27.49 per episode. The average total cost for children below 14 years old was much higher than that for the other age groups. The cost of illness of ILI was, therefore, the reason for the economic burden of influenza patients and their families. This study provides a database for future research and programs, and policies that can be adopted for influenza or ILI in Vietnam.