The thermal degradation behavior of E-CO alternating copolymers submitted to a variety of thermal conditions, both in a vacuum and in an inert atmosphere, has been investigated. The products obtained in the different thermal treatments were analyzed by GC/MS, and the structural changes occurring in the polymer chains were followed by FTIR and UV-vis. The influence of initial degradation reactions on polymer morphology was investigated with DSC, and it was found that thermally induced polymer degradation initiates in the amorphous parts of the samples. The initial reactions involve intramolecular cyclizations which produce cyclopentenone, furanic and oxydrylated structures in the chains, and intermolecular condensations causing cross-linking of polymer chains. Water is the only volatile product formed in this step. When chain scissions start developing, monomers and low molecular weight ketones are obtained as decomposition products. At higher temperatures the degradation embraces the whole polymer and proceeds with a competition of chain scissions, cyclizations, and cross-linking reactions involving macroradicals. The numerous fragments obtained from complete polymer degradation reflect the large structural modifications of the polymer chains.