The thermal stability of Al-Cu-Li alloys is critical for the extreme working conditions in the aircraft industry. The initial stages of thermal oxidation of an industrial AA 2050-T8 Al-Cu-Li alloy were investigated by in situ XPS and ToF-SIMS.Annealing the sample at 200 °C leads to a surface enrichment in metallic Li and Ag. When exposed to oxygen at low pressure (PO2 < 10−6 mbar) a mixed Li-Al oxide layer is formed. Photoemission intensities (recorded at 45° and 90° relative to the surface) are consistent with the formation of a continuous oxide layer for oxygen exposure from 0 to 5000 langmuirs (L). Assuming a homogeneous composition of the oxide layer, its thickness was 9 ± 1 Å at 5000 L. The relative content of Li and Al in the oxide layer evolves from an initial value of 50% to stabilize at 70% of Li above 100 L of oxygen exposure. Simultaneously, the content of Li at the alloy substrate surface is reduced from 10% to 0%. Moreover, specific segregation sites are evidenced by ToF-SIMS three-dimensional chemical mapping. For Li, a homogenous surface distribution while for Mg the accumulation at the grain boundaries were observed. The segregation of Ag at the oxide/alloy interface was confirmed by ToF-SIMS ion depth profiles.