The natural surfaces of many plants and animals provide examples of textures and structures that remain clean despite the presence of environmental fouling contaminants. A biomimetic approach to deciphering the mechanisms used by nature will facilitate the development and application of fouling-resistant surfaces to a range of engineering challenges. This study investigated the mechanism underlying the drag reduction phenomenon that was shown to be responsible for fouling resistance for underwater surfaces. For this purpose, a novel fish-scale-inspired microstructure was shown to exhibit a drag reduction effect similar to that of its natural replica. The primary mechanism through which this occurs is a delayed transition to turbulence. To investigate this mechanism, a Large Eddy simulation was performed at several Reynolds numbers (Re). This analysis demonstrated a peak drag reduction performance of 6.7% at Re = 1750. The numerical data were then experimentally validated through pressure drop measurements performed by means of a custom-built micro-channel. In this case, a peak drag reduction of 4.8% was obtained at Re = 1000. These results suggest a relative agreement between the experimental and numerical data. Taken together, this study advocates that, for the analyzed conditions, drag reduction occurs at low Reynolds numbers. Nonetheless, once flow conditions become more turbulent, the decline in drag reduction performance becomes apparent. [ABSTRACT FROM AUTHOR]