A new surveillance system was developed to detect possible new or emerging infections presenting as undiagnosed serious infectious illness (USII) for use during the London 2012 Olympic and Paralympic Games. Designated clinicians in sentinel adult and paediatric intensive care units (ICU/PICUs) reported USII using an online reporting tool or provided a weekly nil notification. Reported cases were investigated for epidemiological links. A pilot study was undertaken for six months between January and July 2011 to evaluate the feasibility and acceptability of the system. In this six-month period, 5 adults and 13 children were reported by six participating units (3 ICUs, 3 PICUs). Of these 18 patients, 12 were reported within four days after admission to an ICU/PICU. Nine patients were subsequently diagnosed and were thus excluded from the surveillance. Therefore, only nine cases of USII were reported. No clustering was identified. On the basis of the pilot study, we conclude that the system is able to detect cases of USII and is feasible and acceptable to users. USII surveillance has been extended to a total of 19 sentinel units in London and the south-east of England during the London 2012 Olympic and Paralympic Games.