The current work aims at a fundamental understanding of the concept of head loss coefficient, K, of nanofluids flowing in sudden expansionpipe. While so far several articles have applied this concept to the laminar flow regime of water, it is extended here to the mechanics of nanofluids. To describe the flow dissipation, a thermodynamic model is built based on the Second law analysis approach to calculate the overall entropy generation with the assistance of appropriate single-phase models used to get viscosity values of nanofluids. Then, specific values of K can be determined by the integration of entropy generation field. In addition, considering the thermodynamic irreversibility caused by temperature gradients due to heat transfer processes, a new concept of thermodynamic loss coefficient, KE, has been applied to calculate total dissipation. The correlations between K and Reynolds number of sudden expansion flows are also derived. It is interesting to note that the results reveal some striking similarities among nanofluids of various volume concentrations. This unexpected phenomenon shows that the K value is independent of the volume concentration (within the scope of the study). Furthermore, the results show that with an increase in both nanofluid concentration and temperature rise in the heated section, the KE and Nusselt number increases accordingly.