The study focuses on the analysis of the softening effects of the work-hardened aluminum alloy sheets EN AW 5754 H32 1.5 mm thick, through the physical simulation of thermal cycles induced in the material by laser heat treatments (LHTs). A numerical-experimental approach was implemented to define the laser thermal cycles and to subsequently reproduce them on the GleebleTM 3180 physical simulator. The obtained softening was measured by microhardness and metallographic analysis tests. For the definition of laser thermal cycles, preliminary tests with a 2.5 kW CO2 laser source have been realized, and a three-dimensional transient finite element thermal models were developed and calibrated with the experimental results. The investigated laser heat treatment parameters explored thermal cycles with different shape, interaction time, and peak temperature. Physical simulation tests were performed using laser thermal cycles that showed the maximum softening of the aluminum alloy. A three-dimensional transient finite element thermoelectric model was developed to design the shape of the Gleeble specimens, which satisfy the heating and cooling rate required by laser thermal cycles. Results obtained show that it is possible to physically simulate the investigated laser thermal cycles, reducing the cross section of the shaped part of the specimen. Softening effects depend on the thermal cycle shape. Greater softening is observed by increasing the interaction time and the peak temperature, but beyond a peak temperature threshold value, negligible effects are detected.