This study examined the usefulness and challenges of blended learning during the COVID-19 pandemic in Ghana: the mediating role of human resource factors. The study used the explanatory study design from the quantitative approach to gather data from 138 out of 285 postgraduate facilitators on the distance mode. The data collection instrument was self-administered questionnaires and analysis of the data was done with mean and standard deviation as well as Parital Least Square-Structural Equation Modeling. The study found that even though online facilitation was rated higher by facilitators as compared to face-to-face interaction, the facilitators indicated the need for blended learning to minimise challenges associated with either dedicated online facilitation or face-to-face interaction. It was also found that there was a significant relationship between challenges with face-to-face interaction and prospects with online learning, challenges with online learning and prospects for face-to-face interaction. Both remuneration and retrenchment significantly mediated the relationship between challenges with online and blended facilitations. While training significantly mediated the relationship between prospects of online and blended facilitations; work relations failed to achieve a significant mediation influence on the relationship between the prospect of online and blended facilitations. It was recommended that management and human resource managers of postgraduate educational institutions should pay attention to three main human resource factors such as remunerations, training, and retrenchment among facilitators in ensuring smooth running and progress with blended learning within the context of a developing economy.