Thermal and mechanical stresses in stainless steel 316 L plates of gasketed plate heat exchangers (GPHEs) have been assessed with the aid of experiments. Stresses were indirectly determined with the aid of extensometers in critical plate areas. To the best of our knowledge, no experimental analysis of transient thermal loads on GPHE plates has been reported before. Experiments occurred with sudden and gradual heating processes with the aid of strain gauges. The former process implies that hot fluid enters the GPHE branch with the final target temperature, while the latter indicates that the hot fluid is progressively heated to the target temperature. Furthermore, combined mechanical and thermal stresses resulting from in-phase and out-of-phase loads are assessed in single and double operating conditions. Experiments were carried out with two plate thicknesses (0.5 and 0.7 mm). Stresses as obtained from experiments were compared to those provided by models containing simplified geometries and boundary conditions. Mechanical stresses promoted by the pressure difference between GPHE branches mostly affected the distribution area in single configuration. Thermal stresses at the porthole were higher than the ones found at the distribution zones, particularly for thicker plates. Besides, thermal stresses increased in double operation. Sudden heating processes with the system at rest promoted thermal peaking stress in a timescale of seconds, while the timescale to reach peak values by gradually heating the hot fluid is in the order of minutes. The most critical condition would be achieved at the porthole with in-phase loads and in double operation for the given settings.