This study aims to investigate the impact of the High Pressure Selective Catalytic Reduction system (SCR-HP) on a large marine two-stroke engine performance parameters by employing thermodynamic modelling. A coupled model of the zero-dimensional type is extended to incorporate the modelling of the SCR-HP components and the Control Bypass Valve (CBV) block. This model is employed to simulate several scenarios representing the engine operation at both healthy and degraded conditions considering the compressor fouling and the SCR reactor clogging. The derived results are analysed to quantify the impact of the SCR-HP on the investigated engine performance. The SCR system pressure drop and the cylinder bypass valve flow cause an increase of the engine Specific Fuel Oil Consumption (SFOC) in the range 0.3–2.77 g/kWh. The thermal inertia of the SCR-HP is mainly attributed to the SCR reactor, which causes a delayed turbocharger response. These effects are more pronounced at low engine loads. This study supports the better understanding of the operating characteristics of marine two-stroke diesel engines equipped with the SCR-HP and quantification of the impact of the components degradation on the engine performance.