**Background:** In Ethiopia, out-of-school adolescents face greater risks of poor sexual health outcomes, including lower HIV knowledge, unprotected sex, early pregnancy, and violence. Young women involved in sex work and young people with disabilities are particularly marginalized and often excluded from comprehensive sexuality education (CSE), which is predominantly delivered in school settings. This formative research was conducted to inform the design and delivery of out-of-school CSE for these two focal populations as part of a wider initiative supporting UNFPA's guidance on out-of-school CSE in Ethiopia, Ghana, Malawi, and Colombia.
**Methods:** The study employed an integrative framework combining four strands of research conducted between 2014 and 2021. (1) A literature review using the IBSS database with search terms including "adolescen* sexual* Ethiopia" (1,786 results), "out-of-school sexuality Ethiopia" (249 results), "comprehensive sexuality education adolescen* Ethiopia" (207 results), "sex work adolescen* Ethiopia" (764 results), and "sexual* disab* adolescen* Ethiopia" (372 results). (2) Semi-structured in-depth interviews by phone (due to Covid-19 restrictions) with 15 young women involved in sex work and 24 adolescents and young people with disabilities (visual and physical impairments) across Addis Ababa, Hawassa (SNNPR), and Bahir Dar (Amhara). (3) Key informant interviews (KIIs) with 15 government and NGO officials. (4) A mapping exercise and document review of CSE-related stakeholders and interventions. Ethics approval was obtained from the Ministry of Women, Children and Youth Affairs (waiver, July 2020), with oral informed consent from participants over 18 and parental consent with assent for those under 18.
**Key Results:** The situation analysis revealed that poverty and marginalization are key drivers of school dropout. For girls, domestic responsibilities, adolescent pregnancy, and child marriage lead to attrition; for boys, income-earning. Out-of-school adolescents have notably lower HIV knowledge (22% uninformed vs. 6% in-school). Among young women in sex work, most are rural-urban migrants; a key informant estimated around half of 6,000 migrant sex workers in Bahir Dar were aged 15–24. Economic precarity drives HIV exposure risks, as girls can negotiate higher prices for unprotected sex. For young people with disabilities, school dropout rates are five times higher than peers without disabilities; those with walking or communication impairments are 33% and 35% less likely to be enrolled. Only 22% of young people with disabilities reported parents discussing sexual health topics; 52% reported sexual and reproductive health services were unavailable to them. Only 40% of girls with disabilities had heard of STIs vs. 60% of boys. The mapping exercise found that most NGO programming focuses on HIV prevention rather than holistic CSE, and disability-focused organizations largely prioritize in-school adolescents. Government support is fragmented: the National Plan of Action on Persons with Disabilities (2012–2021) mentions sexual and reproductive health, and the HIV/AIDS National Strategy Plan (2021–2025) targets sex workers, but provision is neither widespread nor comprehensive. Key informants reported a disconnect between federal policy commitments and local implementation, exacerbated by under-resourcing and repeated government restructuring (e.g., the Ministry of Women and Social Affairs underwent three name changes between 2019 and 2021).
**Clinical Implications:** The findings highlight that CSE for out-of-school marginalized youth in Ethiopia must go beyond HIV-focused health messaging to address holistic sexuality education, including well-being, human rights, and gender equity. Facilitators require specialized training to address stigma about the sexuality of people with disabilities and sex work, and to create safe, accessible environments. Referral systems to social protection and support services are often missing due to siloed programming. The study underscores the need for structural policy change, better coordination across ministries, and scaled-up urban social protection to reach the most disadvantaged young people and achieve SDG targets on adolescent sexual and reproductive health.