The thermal entropy generation, frictional entropy generation, and exergy efficiency of CoFe2O4/water nano-fluids flow in a tube have been analyzed experimentally and the obtained data is predicted with ANFIS and MLP algorithms. The CoFe2O4 nanoparticles were developed through the chemical coprecipitation procedure and then characterized with XRD and TEM instruments. The thermophysical properties of CoFe2O4/water nanofluids were analyzed with various instruments in the temperature range from 20 degrees C to 60 degrees C and in the volume concentration range from 0.25% to 1.25%, respectively, and then entropy and exergy efficiency experiments were conducted, while the CoFe2O4/water nanofluids flow in a tube. Results show, the thermal entropy generation is lowered by 31.80% and the frictional entropy generation is larger by 240.17%, and the exergy efficiency is higher by 17.58% at phi = 1.25% and at a Reynolds number of 19301, over base fluid. Results also shows, the ANFIS model predicts very high accuracy for the experimental data compared to the MLP-ANN model with a correlation coefficients of 0.99798, 0.9944, and 0.99427 for thermal entropy, frictional entropy and exergy efficiency, respectively. The new thermal entropy, frictional entropy and exergy efficiency correlations were presented from the experimental data.