As health-related big data research (HRBDR) has drastically increased over the last years due to the rapid development of big data analytics, a range of important ethical issues are raised. In this study, a systematic literature review was conducted. Several and interesting results emerged from this review. The term ″big data″ has not yet been clearly defined. The already existing ethical principles and concepts need to be revisited in the new HRBDR context. Traditional research ethics notions like privacy and informed consent are to be reconsidered. HRBDR creates new ethical issues such those related to trust / trustworthiness and public values such as reciprocity, transparency, inclusivity and common good. The implementation of dynamic consent rather than broad consent is currently highlighted as the more satisfying solution. Ethical review committees in their current form are ill-suited to provide exclusive ethical oversight on HRBDR projects. Expanding Ethical Review Committees' purview and members' expertise, as well as creating novel oversight bodies by promoting a co-governance system including public and all the stakeholders involved are strongly recommended. The mechanism of ″social licence″, that is, informal permissions granted to researchers by society, can serve as a guideline. High-stakes decisions are often made under uncertainty. Machine learning algorithms are highly complex and in some cases opaque, and may yield biased decisions or discrimination. Improved interdisciplinary dialogue along with considering aspects like auditing, benchmarking, confidence / trust and explainability /interpretability may address concerns about HRBDR ethics. Finally and most importantly, research ethics shifts towards a population-based model of ethics.