The maturation from reticulocyte (immature red blood cell) to erythrocyte (mature red blood cell) includes the loss or decreased expression of cell surface molecules through exosome formation and secretion. Identifying the molecules lost and the molecular events involved is important to our understanding of this final stage of erythropoiesis and of diseases where it is deranged. Also, the presence of certain cell surface molecules is likely responsible for the invasion of certain malaria parasites into reticulocytes. Using a global proteomics approach, we identified proteins potentially lost during and/or involved in the reticulocyte maturation process. The reticulocyte proteome has not yet been published, as previous such studies have focused on the mature erythrocyte. Membrane-rich fractions were fractionated by electrophoresis followed by analysis with tandem mass spectrometry. Seven hundred forty four proteins were identified in the reticulocyte-rich membrane fraction, 192 proteins in the erythrocyte-rich membrane fraction, with 157 common to both fractions. Many of the proteins found uniquely in the reticulocyte were associated with structures known to be in reticulocytes (mitochondria, Golgi). Additional proteins detected are or may be specifically involved in vesicle trafficking, a process important in the maturation process. A number of unique plasma membrane proteins were also identified. These results provide the groundwork for future targeted studies to improve our understanding of the mechanism of reticulocyte maturation and the role of reticulocytes in disease.