INTRODUCTION: There are suggestions that virus co-infections may influence the clinical outcome of respiratory virus illness. We performed a systematic review of the literature to summarise the evidence. METHODS: MEDLINE, EMBASE, Ovid and WEB of Science databases, major organisation websites and reference lists of published studies were searched. The quality of studies was assessed using the STROBE tool (von Elm et al., 1) Individual study data was analyzed using odds ratios and 95% confidence intervals as a measure of association between exposure (co-infection), patient outcome and results summarised using forest plots and tables RESULTS: Nineteen (19) studies from all over the world were identified and included in the review. Most of the studies 73.7% (14/19) recruited children ≤6 years old. Evidence on the role of co-infection in increasing disease severity was inconclusive. In five out of eight studies, co-infection significantly increased risk of admission to general ward (OR: 2.4, 95% CI: 1.3 - 4.4, p = 0.005; OR: 2.4, 95% CI: 1.1 - 7.7, P = 0.04; OR: 3.1, 95% CI: 2.0 - 5.1, p =