PURPOSE: Social determinants of health, including food insecurity, housing instability, social isolation, and unemployment are important drivers of health outcomes and utilization. To inform implementation of social needs screening and response protocols, there is a need to identify the associated costs in routine primary care encounters. METHODS: We interviewed key stakeholders in four diverse community health centers that had adopted a widely used social needs screening and response protocol. We evaluated costs using an activity-based costing tool across both the initial implementation phase and ongoing maintenance phase. RESULTS: Clinic costs were associated with workforce development, planning, and electronic health record integration. These initial implementation costs varied by site ($6,644-$49,087). On a per-patient basis, ongoing maintenance costs ranged from $9.76 to $47.98. CONCLUSION: Our findings can aid in designing reimbursement mechanisms tied to social needs screening and response to accelerate translational efforts and promote health equity.