Massive open online courses (MOOCs) provide accessible and engaging information for Physical Therapy and Occupational Therapy students. The objective of this research was to determine the usefulness in improving academic performance and empathy in health sciences undergraduates, and to test a hypothetical model through structural equation analysis. This research was carried out using a descriptive and quasi-experimental design. It was conducted in a sample of 381 participants: 176 used a MOOC and 205 did not. The results of the Student’s t-test showed statistically significant differences in academic performance between the groups in favor of those students who had realized the MOOC. Participants carried out an evaluation rubric after taking MOOC. Statistically significant differences in empathy were also obtained between the pre (X = 62.06; SD = 4.41) and post (X = 73.77; SD = 9.93) tests. The hypothetical model tested via structural equation modeling was supported by the results. Motivation for the MOOC explained 50% of the variance. The MOOC (participation and realization) explained 58% of academic performance, 35% of cognitive empathy and 48% of affective empathy. The results suggest an association between higher realization and participation in a MOOC and higher levels of academic performance, and cognitive and affective empathy.