The thermal deoxidation procedure of GaSb(100) substrates has been investigated with in-situ reflectance difference spectroscopy (RDS). The "epi-ready" substrates were loaded in a metal-organic vapor phase epitaxy (MOVPE) reactor either "as-supplied" or after etching with HCl to remove the native oxide layer. Annealing between 475-575 degrees C and in-situ monitoring reveals RDS features associated with the surface morphology and the development of oxide desorption. This process is supported by molecular hydrogen utilized as carrier gas. Photoemission spectroscopy was applied to benchmark the surface of selected samples with regard to the electronic structure and the chemical composition during the deoxidation of GaSb(100) substrates. Based on the in-situ and UHV data, a model of the oxide desorption process and recommendations for the GaSb substrate deoxidation procedure in MOVPE environment are proposed. (c) 2004 Elsevier B.V. All rights reserved.