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Background: Despite the rise of big-team science and multiinstitutional, multidisciplinary research networks, little research has explored the unique challenges that large, distributed research networks face in ensuring the ethical and responsible conduct of research (RCR) at the network level. Methods: This qualitative case study explored the views of the scientists, engineers, clinicians, and trainees within a large Engineering Research Center (ERC) on ethical and RCR issues arising at the network level. Results: Semi-structured interviews of 26 ERC members were analyzed and revealed five major themes: (1) data sharing, (2) authorship or inventorship credit, (3) ethics and regulation, (4) collaboration, and (5) network leadership, norms, and policy. Interviews revealed cross-laboratory differences and disciplinary differences as sources of challenge. Conclusions: This study illuminates ethical challenges that a large, multi-institutional research network is likely to face. Research collaboration across disciplines, laboratories, and institutions invites conflict over norms and practices. Network leadership requires anticipating, monitoring, and addressing the ethical challenges in order to ensure the network’s ethical and responsible conduct of research and optimize research collaboration. Studying perceived ethical issues that arise at the meso-level of a research network is essential for understanding how to advance network ethics.