As a partial condition for the successful completion of school, and for certification reasons, undergraduate distance education students in Ghanaian universities are required to conduct research work. Due to the mode of teaching and learning activities, it appears such students are at a disadvantage. In this study, we examined the challenges distance education students encounter in conducting their research work in two universities in Ghana. A cross-sectional survey was conducted using 866 distance education students sampled from the study centres across the country. Results from a confirmatory factor analysis, using 5,000 bootstrap samples, revealed challenges from the students, supervisors and the institutions. Based on our results, we recommend that there should be structured policies by university management and supervisors to relieve students of the challenges they encounter when conducting their research work. The study also encouraged students to devote the needed time, commitment and motivation to complete their research work on time. Suggestions for further studies were made based on the findings.