Crop losses, especially along the post-harvest value chain, have been identified as one of the major causes of food shortages in most developing countries including Liberia. Rice farmers often record a great amount of loss which translates to a waste of resources, a reduction in their income, and ultimately their welfare. This study examined the effects of post-harvest losses on the profitability of rice production among smallholder rice farmers in Liberia. The analytical tools used in the study include descriptive statistics, gross margin analysis, and multiple regression models. The gross margin analysis results revealed that the average gross margin with post-harvest loss was 3,512.475 Liberian Dollars, lower than the average gross margin without post-harvest 8,826.114 Liberian Dollars. This implied a 39.79% reduction in the gross margin of rice farmers valued at over 2.8 million Liberian Dollars. The results also found the Value of Post-Harvest Loss, Market Participation Rate, Quantity Harvested, Quantity sold, and Education Level significantly affect the per-capita gross margin of farmers. The study recommends that farmers engaging in rice production be adequately trained on post-harvest crop handling techniques whereas, priority be given to investment in post-harvest processing technologies and the establishment of processing industries especially in the major production areas.