Background: Organ donation rates in India are among the lowest globally. The complex interplay of social, religious, and media influences behind organ donation in today's social milieu is not fully understood. Health-care professionals are in a unique position to influence popular perception on organ donation through their practices. Objectives: The objective of this study was to explore organ donation-related perceptions and practices among health science students from southern India. Methods: A cross-sectional questionnaire-based, online descriptive study was carried out among undergraduate health science students from the medical, nursing, and allied health science streams in Coimbatore, western Tamil Nadu. A total of 618 respondents participated in the online survey conducted during the summer 2021. Statistical analysis was done using IBM SPSS version 27 statistical package. Results: The general awareness levels and perceptions regarding organ donation were fairly high, and 83.1% were interested in becoming an organ donor. Even though a sizable proportion (37.4%) were ready to pledge right away, many did not know how to take the next step - the actual pledging for organ donation. Apprehensions relating to organ donation fell under few major themes - concerns of misuse of organ donation platforms for monetary gains; cumbersome legal procedures; family, social, and religious beliefs; and influences of popular media. Conclusions: Despite a fair degree of knowledge, the practice of organ donation seems to be relatively low among the participants, owing to a multitude of reasons. If enabled appropriately, health science graduates would be the perfect ambassadors for promoting organ donation in the society.