Few studies have investigated whether harmonious passion (HP) and obsessive passion (OP) make a distinctive contribution to explaining individual differences in knowledge management through self-regulation in e-learning contexts. This study aimed to identify four types of passion (internal HP, external HP, internal OP, and external OP) in e-learning and, further, to examine the relationships between different types of passion, self-regulation, and knowledge management in e-learning. The participants were 1209 college students. Three 4-point Likert scales were employed to measure the concerned variables and structural equation modeling was employed to examine the proposed model. The findings revealed that the four types of passion were interrelated and that the proposed model was a good-fit model. Specifically, self-regulation mediated the influence of passion on knowledge management in e-learning. However, HP and OP predicted self-regulation and knowledge management in the opposite way, and HP played a more crucial role than OP in e-learning. The result in this study not only support the two-dimensional model of passion but also suggest that the four types of passion, though positively correlated, interact in ways that have different effects on college students’ self-regulation and knowledge management in e-learning.