Abstract This paper describes a set of experimental tests carried out to better understand the thermal behavior of Lithium-ion batteries under load and the capability of various cooling fluids in maintaining the working conditions within a safe range for the cells. Despite several theoretical models are available in the literature, very few experimental data are reported. Different types of cells have been analyzed. The generation of hot spots has sometimes been registered, their occurrence being independent of cell geometry and size; instead, the battery's history and age, appeared the main factors in determining the onset of hot spots on the surface of the cell. Two experimental rigs have been set up to test the capability of different cooling fluids in removing the surplus heat generated in a Li-ion battery module, where the cells of interest have been replaced with electrically heated elements with the same thermal characteristics of the cells. It was thus possible to safely investigate “extreme” operating conditions, where the occurrence of a thermal runaway is possible. Among the tested fluids, air was unable to adequately limit the surface temperature increase, while a perfluorinated polyether, allowed to work within the optimal temperature range, even under severe operating conditions.