Abstract Sickle cell disease (SCD) is a major contributor to child morbidity and mortality. Life expectancy of babies with SCD varies widely depending on geographic location. In the USA, universal newborn screening (NBS) facilitates early diagnosis and prompt linkage to care with overall survival rate in SCD children greater than 94%. In Sub- Saharan Africa (SSA) approximately 90% of the children born annually with SCD will die before their fifth birthday, often undiagnosed. The absence of early diagnosis through laboratory-based NBS program is a major barrier to implementation of timely preventive measures in SSA. Emergent, novel, inexpensive, point-of-care tests (POCTs), with analytic characteristics and field-tested performance comparable to laboratory methods offer intriguing options for early diagnosis of SCD in primary health centers (PHCs). Our study objective is to use a type-2 hybrid implementation-effectiveness design to assess and pilot a SCD-POCT model in one urban and one rural PHC over 6 months in Sierra Leone where our extant SCD health systems strengthening and human capacity building research program is housed. Our rationale is that early SCD diagnosis in neonates demonstrably decreases morbidity and mortality rates considerably in the first 5 years of life. In this feasibility study, the research aims include developing and assisting PHCs in implementing the model; evaluating processes/determinants of model implementation; and evaluating the model’s effectiveness, acceptability and effects on provider and client outcomes. Using implementation science frameworks, our research team will iteratively engage key stakeholders to inform the development of the PHC-based SCD-POCT model. The evidence-informed nurse champion platform will frame the implementation model and will include pre/post-test counseling, nurse administered POCT and care coordination. Nurses will complete a comprehensive provider training program prior to implementing the model. Three specific aims undergird our study: (1) Assess barriers and facilitators to primary health center provision of SCD-POCT with a nurse champion model; (2) Finalize an implementation plan for the intervention using Implementation Mapping and stakeholder input; and (3) pilot the nurse champion model in two primary health centers and evaluate determinants and implementation costs. The process of developing and implementing the model will be described using implementation science frameworks, ethnographic observations, qualitative interviews and implementation mapping to identify barriers/enablers. Nurse and client outcomes will be assessed by focus groups and in-depth interviews. Model implementation will be assessed qualitatively and quantitatively. Acceptability, barriers, and enablers will be examined qualitatively based on focus group and interview responses. A preliminary costing assessment will consider the nurses and research study financial outlays. We expect our study to establish the...