Fused or sintered Cu nanoparticle structures are potential alternatives to solder for ultrafine pitch flip chip assembly and to sintered Ag for heat sink attach in high-temperature micro-electronics. Meaningful testing and interpretation of test results in terms of what to expect under realistic use conditions do, however, require a mechanistic picture of degradation and damage mechanisms. As far as fatigue goes, such a picture is starting to emerge. The porosity of sintered nanoparticle structures significantly affects their behavior in cycling. The very different sensitivities to parameters, compared to solder, mean new protocols will be required for the assessment of reliability. This study focused on fatigue in both isothermal and thermal cycling. During the latter, all damage occurs at the low-temperature extreme, so life is particularly sensitive to the minimum temperature and any dwell there. Variations in the maximum temperature up to 125 °C did not affect, but a maximum temperature of 200 °C led to much faster damage. Depending on particle size and sintering conditions, deformation and damage properties may also degrade rapidly over time. Our picture allows for recommendations as to more relevant test protocols for vibration, thermal cycling, and combinations of these, including effects of aging, as well as for generalization of test results and comparisons in terms of anticipated behavior under realistic long-term use conditions. Also, the fatigue life seems to vary with the ultimate strength, meaning that simple strength testing becomes a convenient reference in materials and process optimization.