Background: Humanitarian health care organizations and health workers working in contexts of armed or violent conflict experience challenges in fulfilling ethical obligations and humanitarian principles. To better understand the types of challenges experienced in these contexts, we conducted a systematic literature review. Methods: A broad search strategy was developed for English language publications available in PubMed, Ovid/ EMBASE, and Scopus. The search relied upon three key concept blocks: conflict settings, humanitarian or relief organizations, and non-clinical or non-military ethics. To be included, publications had to (1) refer implicitly or explicitly to ethics and/or humanitarian principle(s), (2) relate to non-military relief work in active conflict or conflictaffected settings, (3) relate to organizational mission and/or delivery of services, and (4) relate to events after 1900. Records were qualitatively analyzed using an emergent thematic analysis approach that mapped challenges onto recognized ethical obligations and humanitarian principles. Results: A total of 66 out of a possible 2077 retrieved records met inclusion criteria. The most frequently noted ethical challenges for organizations working in conflict settings were (1) providing the highest attainable quality of care, (2) protecting workers, and (3) minimizing unintended harms. The humanitarian principle most frequently noted as challenging to uphold was neutrality (the duty that humanitarian actors must not take sides in a conflict). Ethical challenges and humanitarian principles were commonly co-coded. For example, the challenge of providing the highest attainable quality of care frequently intersected with the humanitarian principle of humanity. Conclusions: By categorizing the types of ethical challenges experienced by humanitarian care organizations, this review can help organizations anticipate issues that might arise in conflict settings. The identified relationships between ethical challenges and humanitarian principles suggests that frameworks and guidance for ethical decision-making, if adapted for conflict settings, could support organizational capacity to fulfill ethical and humanitarian commitments.