Increasing pressure is being placed on the marine industry to address ship emissions, regulations to govern the efficient operation of ships in the form of the Energy Efficiency Design Index (EEDI) and Energy Efficiency Operation Index (EEOI) have recently come into force. All aspects of ship design and operation that impact the energy efficiency of ships are subject to revaluation. This paper investigates the detrimental effects of biofouling on the performance of Potsdam Propeller Test Case (PPTC) propeller using Computational Fluid Dynamics (CFD). A previously-developed CFD approach for approximating the surface roughness due to biofouling has been applied in order to predict the effects on propeller characteristics. The roughness effects of a typical coating and different fouling conditions on the propeller performance were predicted for various advance coefficients. The effect proved to be drastic with the most severe fouling condition resulting in a 11.9% efficiency loss at J = 0.6 ranging to an alarming 30.3% loss at J = 1.2 compared to the smooth condition. The study acts as a proof of concept for the proposed CFD assessment method which can be used as a very practical approach to predicting the impact of realistic fouling conditions on propeller characteristics and energy efficiency.