Objective— The chemokine receptor CX ₃ CR1 is an inflammatory mediator in vascular diseases. On platelets, its ligation with fractalkine (CX ₃ CL1) induces platelet activation followed by leukocyte recruitment to activated endothelium. Here, we evaluated the expression and role of platelet-CX ₃ CR1 during hyperlipidemia and vascular injury. Methods and Results— The existence of CX ₃ CR1 on platelets at mRNA and protein level was analyzed by RT-PCR, quantitative (q)PCR, FACS analysis, and Western blot. Elevated CX ₃ CR1 expression was detected on human platelets after activation and, along with increased binding of CX ₃ CL1, platelet CX ₃ CR1 was also involved in the formation of platelet–monocyte complexes. Interestingly, the expression of CX ₃ CR1 was elevated on platelets from hyperlipidemic mice. Accordingly, CX ₃ CL1-binding and the number of circulating platelet–monocyte complexes were increased. In addition, CX ₃ CR1 supported monocyte arrest on inflamed smooth muscle cells in vitro, whereas CX ₃ CR1-deficient platelets showed decreased adhesion to the denuded vessel wall in vivo. Conclusion— Platelets in hyperlipidemic mice display increased CX ₃ CR1-expression and assemble with circulating monocytes. The formation of platelet–monocyte complexes and the detection of platelet-bound CX ₃ CL1 on inflamed smooth muscle cells suggest a significant involvement of the CX ₃ CL1–CX ₃ CR1 axis in platelet accumulation and monocyte recruitment at sites of arterial injury in atherosclerosis.