A comparative study of the behaviour of Iodine and Caesium in uranium oxide was conducted. UO2 samples implanted with Iodine or Caesium underwent thermal treatment (4 h at 900 °C or 1 h at 1200 °C) in a controlled atmosphere (Ar+0.03% H2O/H2). Thereafter, the samples were analysed using a range of experimental techniques to study their structural and chemical evolution. Additionally, thermodynamic calculations were performed in order to optimize heat treatment conditions before performing tests, and to assist in the interpretation of results afterwards. The sample characterizations after thermal treatments reveal the following differences in the behaviour of Iodine and Caesium in UO2 during heat treatment: i) precipitates are mainly observed in the case of samples implanted with Iodine, in contrast to Cs, where bubbles are mainly observed and ii) a very high release rate in the case of Caesium, unlike Iodine.