In dry storage conditions, the accidental scenario takes into consideration a defective nuclear fuel rod reacting with the atmosphere. In order to gain information on French nuclear fuel, a new experimental setup named CROCODILE was developed to perform oxidation experiments in hot cells on defective fuel rodlets with controlled temperature and atmosphere. The first test was performed at 623 K in air with a rodlet taken from a four-cycle mixed-oxide fuel rod in which defects were simulated by drilling holes in the cladding. After 139 h of oxidation, significant degradation was observed with the development of radial and axial cracks. At this point, the experiment was stopped and the rodlet was analyzed. The main features observed were (a) a significant strain in the cladding around the cracks, which resulted in the detachment of fuel fragments; (b) no evidence of hydride accumulation in the cladding; and (c) a heterogeneous propagation of the oxidation front in the nuclear ceramic. The influence of the simulated defect is discussed and the use of a round defect is examined.