This paper describes the experimental investigations conducted on a closed loop pulsating heat pipe (CLPHP) for assessing the thermal performance. The pulsating heat pipe has a single closed loop made of copper. The working fluids used are water and titanium dioxide nanofluids with varying concentrations of TiO2 nanoparticles (1.5% and 1%) on weight basis. The TiO2 particles are mixed in water to form a stable suspension using a sonicator. The heat input is varied between 40 W and 100 W in steps of 20 W. All experiments are conducted in the bottom heating mode (evaporator at the top) in the vertical and horizontal orientations. The parameters considered for evaluating the thermal performance are the temperature difference between evaporator and condenser, thermal resistance, heat transfer coefficient, and thermal conductivity. The results of the investigation reveal that the vertical orientation and increase in nanoparticle concentration favors better heat transfer performance of the single closed loop pulsating heat pipe.