This study investigated the coupled influences of the content and methylene blue value (MBV) of microfines on the comprehensive performance of manufactured sand concrete. The results show that microfines with a low MBV improve the workability of fresh concrete and the compactness of hardened concrete, thus improving certain properties of the concrete. In contrast, microfines with a high MBV are detrimental to frost resistance and shrinkage. Furthermore, the requirements regarding the allowable content of microfines can be relaxed depending on the associated MBV in order to make full use of microfines in manufactured sand concrete. Finally, this study calculates the coefficient of the coupled effects of the content and MBV of microfines on the performance of manufactured sand concrete based on the correlation theory and provides the basis for updating the content and MBV requirements for microfines in actual engineering. Sand can be replaced with microfines in traditional construction, transportation engineering and bridge engineering, thereby alleviating shortages of river sand.