Despite recognition that health research is an imperative to progress toward universal health coverage, resources for health research are limited. Yet, especially in sub-Saharan Africa, more than 85% of the resources available for health research are spent on answering less relevant research questions. This misalignment is partially due to absence of locally determined health research priorities. In this study, we identified health research priorities which, if implemented, can inform local interventions required to accelerate progress toward universal health coverage in Somalia. We adapted the child health and nutrition research initiative method for research priority setting and applied it in 4 major phases: (1) establishment of an exercise management team, (2) a web-based survey among 84 respondents to identify health research questions; (3) categorization of identified health research questions; and (4) a workshop with 42 participants to score and rank the identified health research questions. Ethical approval was received from ethics review committee of the London School of Hygiene and Tropical Medicine (Ref:26524) and the Somali Research and Development Institute (Ref: EA0143). Two hundred and thirty-one unique health research questions were identified and categorized under health systems, services and social determinants (77), communicable diseases (54), non-communicable diseases (41) and reproductive, maternal, new-born, child, adolescent health and nutrition (59). A priority score ranging from 1 to 9 was assigned to each of the questions. For each category, a list of 10 questions with the highest priority scores was developed. Across the four categories, an overall list of 10 questions with the highest priority scores was also developed. These related to bottlenecks to accessing essential health services, use of evidence in decision making, antimicrobial resistance, distribution and risk factors for non-communicable diseases, post-traumatic stress disorder and factors associated with low antenatal care attendance among others. The developed priority research questions can be used to focus health research and to inform appropriation of health research resources to questions that contribute to generation of local health system knowledge which is required to accelerate progress toward universal health coverage in Somalia. The Somalia national institute of health should set up a consortium for provision of technical and financial support for research addressing the identified priority research questions, establish a mechanism to continuously monitor the extent to which new health interventions in Somalia are informed by knowledge generated through conducting prioritized health research and prioritize interventions aimed at strengthening the broader national health research system for Somalia.