An experimental study is reported about a copper closed-loop flat plate pulsating heat pipe tested in both horizontal and vertical -bottom heated mode- orientations and at two cold source temperatures (20 °C and 40 °C); several working fluids were tested after having modified of their surface tension compared to pure water, verified through dedicated sessile droplets test bench. After which, tests were performed using pure water, pure ethanol, binary aqueous mixtures (water/ethanol, water/butan-1-ol and water/butan-2-ol, the last two being self-rewetting fluids) and water/surfactant mixtures (Tween® 20 and Tween® 40) as working fluids. The thermal performances of the device tested in horizontal orientation were significantly better for the aqueous mixtures such as water/ethanol and water/butan-2-ol than for the others (with values of thermal resistances down to 63%, and 52%, respectively, lower than those of pure water at 20 °C cooling temperature). Concerning pure fluids, the device presents severe temperature and pressure instabilities. Water with surfactants also presents enormous instabilities, calling into question the interstitial influence of the tested surfactants in the hydraulic slug flow pattern occurring in horizontal inclination. The results in vertical orientation, although often studied in the literature, are less conclusive and more difficult to analyze given that surface tension effects are less influential compared to the gravity effects in the annular or bubbly flow patterns occurring in this operating mode. Finally, zeotropic mixtures with butan-2-ol and ethanol performing very similarly, and considering their identical surface tension, the expected rewetting effect of SRWF is not proven, and may not even explain improved FPPHP operation, which is rather assumed to be largely caused by enhanced wettability or increased (∂P/∂T)sat.