The COVID-19 pandemic has generated mass infections, staggering death totals, social disruption, and economic fallout not seen since the 1918 flu pandemic. Public health experts have identified COVID-19 as the most formidable health crisis of the twenty-first century. Mississippi (MS) has experienced significant increases in COVID-19 cases and deaths while trailing nearly all other states in coronavirus testing. These challenges have been magnified by MS’ poverty rates, pronounced health disparities, longstanding racial-ethnic stratification, and rural remoteness. These factors have long placed MS atop state rankings in negative mental health indicators. Under normal circumstances, MS faces formidable mental health (MH) adversities, substance use disorder (SUD) vulnerabilities, and co-occurring disorder (COD) problems. The COVID-19 pandemic, coupled with social distancing directives, shelter-in-place orders, and mass unemployment, has raised these threats to critical levels in the nation’s poorest state. Given these challenges, the Mississippi Department of Mental Health (DMH) proposes the MERC-19 (Mississippi Emergency Response to COVID-19) project. MERC-19 proposes a three-pronged approach to enhance and expand the continuum of care for people with SMI, SED, SUD, and COD while also improving service delivery to frontline workers directly battling this pandemic. MERC-19’s use of a three-pronged approach will enable MS to (1) to ensure that community-based services are provided with an emphasis on telehealth offerings and ensure that they are initiated and expanded for a wide range of feasible MH, SUD, and COD services provided to clients of CMHCs funded by this initiative; (2) facilitate the expansion of sustainable tele-MAT capacities statewide with special attention to socially isolated current or prospective MAT clients located in remote rural areas; (3) support the proactive delivery of MH and SUD services to healthcare professionals, crisis hotline workers, and first responders who have been traumatized by their efforts to combat COVID-19. Culturally competent service delivery will also be enlisted to reduce COVID-related health disparities that have already emerged. Current data supports the prioritization of African American adults and residents living in remote areas lacking treatment services. Planned evidence-based interventions include, among others, Peer Support Services, Mobile Crisis Teams, Crisis Stabilization, Wraparound Facilitation, Trauma-Focused Cognitive Behavioral Therapy, Assertive Community Treatment, Intensive Care Management, Community Outreach and Recovery Support Teams, Outpatient Therapy, Supported Employment, and Supported Housing, all delivered with a focus on telehealth/telemedicine modalities wherever feasible. High-risk and rural areas of the state will also be subject to a targeted communication campaign designed to help the most vulnerable residents, including healthcare workers. MERC-19 promises to enhance COVID-related treatment and recovery services rapidly while improving the quality of life among MS residents in the wake of this public health crisis.