To test our hypothesis that fentanyl and morphine have distinct effects on neuroinflammatory signaling within the context of HIV, we tracked changes in the concentration of nine chemokines—CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL11/eotaxin, CCL17, CCL22, CXCL13 and CXCL10—in response to fentanyl or morphine exposure (five-day continuous delivery) in mice with or without EcoHIV (HIV+ or HIV−) infection. Here, CCL4 is linked to infection.