Platelets are small anucleate blood cells, produced from their precursor cells megakaryocytes, and have a primary role in haemostasis; following tissue trauma and exposure of the subendothelial matrix, a coordinated series of events enables the formation of a platelet plug, and central to this process are the platelet surface receptors. Two major receptors are the glycoprotein (GP) Ib-V-IX complex, composed of GPIbα, GPIbβ, GPIX and GPV, and integrin αIIbβ3, composed of αIIb and β3, that bind collagen bound von Willebrand factor and fibrinogen, respectively. These receptors are responsible for initiating, driving, and amplifying essential platelet function and therefore mediating haemostasis. However, the mechanisms by which platelets control their surface receptor expression remains unclear. Here, the role of clathrin mediated endocytosis (CME) proteins was investigated using both a pharmacological and genetic approach. We show that upon activation of mouse platelets, individual receptors and subunits are regulated independently, and when activated via GPVI but not the PAR receptors, inhibiting dynamin-2 and clathrin impairs this. We also show that the activity of the small GTPase Rab5 differentially regulates different receptors in the human megakaryocytic cell line Dami. Taken together, we provide a role for CME proteins in the regulation of platelet receptor trafficking.