This case study explores ethical issues that relate to the use of Smart Infor-mation Systems (SIS) in human brain research. The case study is based on the Human Brain Project (HBP), which is a European Union funded project. The project uses SIS to build a research infrastructure aimed at the advancement of neuroscience, medicine and computing. The case study was conducted to assess how the HBP recognises and deal with ethical concerns relating to the use of SIS in human brain research. To under-stand some of the ethical implications of using SIS in human brain research, data was collected through a document review and three semi-structured interviews with partic-ipants from the HBP. Results from the case study indicate that the main ethical concerns with the use of SIS in human brain research include privacy and confidentiality, the security of personal data, discrimination that arises from bias and access to the SIS and their outcomes. Furthermore, there is an issue with the transparency of the processes that are involved in human brain research. In response to these issues, the HBP has put in place different mechanisms to ensure responsible research and innovation through a dedicated pro-gram. The paper provides lessons for the responsible implementation of SIS in research, including human brain research and extends some of the mechanisms that could be employed by researchers and developers of SIS for research in addressing such issues.