Background: Suicide is a leading cause of death among American Indian youth, reflecting the intergenerational consequences of colonization, historical trauma, racism, and the chronic underfunding of critical health and social services in Native communities. American Indian values, spiritualities, and cultural practices promote the physical, social, and emotional health of Native people, and there is a need for community-based case management approaches and culture-informed behavioral interventions that build from this strength. Cost and cost-effectiveness estimates are critical for policymakers in Tribal communities considering investing in such services. Objectives : Our objective will be to estimate the cost and cost-effectiveness for community-based paraprofessionals to deliver three preventive services to American Indian youth (aged 10-29): case management, New Hope (a brief intervention to reduce immediate suicide risk) and Elders' Resilience (a brief intervention incorporating Elders to increase connectedness, self-esteem, and cultural identity). Methods : We will conduct an economic evaluation as part of a Sequential Multiple Assignment Randomized Trial in a rural, reservation-based American Indian community in the Southwest. A five-year time horizon, societal perspective, and 3% discount rate will be used. An ingredients-based approach will estimate fixed program costs (e.g., intervention development, shared overhead) and variable program costs (e.g., labor and intervention delivery). Additional costs to the participants and healthcare payer will be estimated. Data collection methods will include key informant interviews, activity logs, expenditure reports and records review, direct observation, and medical chart review. Total cost estimates for each service will be divided by the respective numbers of participants reached to estimate relative cost-efficiency. Primary and secondary outcomes will be quality-adjusted life years and suicidal ideation, respectively. Incremental cost effectiveness ratios will be estimated. Discussion: We will develop much-needed estimates of the cost and cost-effectiveness of delivering community-based, paraprofessional-delivered case management and culture-informed suicide prevention interventions in a rural, reservation-based American Indian community in the Southwest. These estimates will fill a key gap for Tribal policymakers considering comparable services for their communities. Trial Registration: Clinical Trials NCT03543865, June 1, 2018.