Effects of initial stress-strain states on irradiation performance of monolithic fuel plates were studied. The monolithic fuel plates consist of a high density low enrichment U-Mo fuel that is encapsulated in an Aluminum cladding. Because the fabrication involves multiple stages, there are concerns, if the irradiation performance of the plates is affected by the pre-irradiation stress-strain states. To investigate these concerns, a representative plate was evaluated for distinct initial stress-strain states. First, the foil preparation stage by co-rolling process was simulated. For this, a scaled version of the process was simulated to calculate the stress-strain profiles. These profiles were then used to incorporate initial states for the HIP process. Additional HIP simulations were also considered to evaluate the cases with stress-free foils prior HIP bonding. For the simulation of HIP process with initially stress-free co-rolled foils, several bonding temperatures were considered. Finally, the irradiation processes were simulated for all cases with distinct pre-irradiation stress-strain states. The stress-strain fields from the fabrication process were used to incorporate the initial states for the irradiation simulations. The resulted distortions, stress-strain fields and temperature profiles were extracted at the selected locations. Finally, a comparative evaluation was made to determine the sensitivity of the plate’s performance to the pre-irradiation stress-strain states. The irradiation simulations have revealed that the fabrication stresses in the fuel would be relieved relatively fast in reactor. The fuel foil would be essentially stress-free during irradiation. The stresses however, would develop at the shutdown stage. For the cladding material, the stresses continue to increase and additional plastic strains are generated as a result of fuel swelling. The study indicated that the stress-strain fields of the plates during irradiation are not affected by the initial stress state of the plates.