CFD technique was employed to investigate the effect of surface roughness on the mean pressure coefficients of a full-scale cooling tower. Six kinds of surface roughness with smooth surface and varying roughness heights, as covered by the design code, were studied for a full-scale cooling tower. The numerical results were compared with the wind tunnel and full-scale measurement results from published works. It has been shown that, when full-scale-based CFD simulation successfully circumvents the Reynolds similitude, the smooth tower section has a large mean wind pressure coefficient than the rougher tower sections. It is therefore concluded that the real surface roughness must be reproduced in the evaluation of the mean wind pressure coefficient of cooling towers.