Vaccine hesitancy and refusal remain a major concern for healthcare professionals and policymakers. Hence, it is necessary to ascertain the underlying factors that promote or hinder the uptake of vaccines. Authorities and policy makers are experimenting with vaccine promotion messages to communities using loss and gain-framed messages. However, the effectiveness of message framing in influencing the intention to be vaccinated is unclear. Based on the Theory of Planned Behaviour (TPB), this study analysed the impact of individual attitude towards COVID-19 vaccination, direct and indirect social norms, perceived behavioural control and perceived threat towards South Indian millennials' intention to get vaccinated. The study also assessed the effect of framing vaccine communication messages with gain and loss framing. Data was collected from 228 Millennials from South India during the COVID-19 pandemic from September to October 2021 and analysed using PLS path modelling and Necessary Condition Analysis (NCA). The findings reveal that attitudes towards vaccination, perceived threat and indirect social norms positively impact millennials' intention to take up vaccines in both message frames. Further, independent sample t-test between the framing groups indicate that negative (loss framed message) leads to higher vaccination intention compared to positive (gain framed message). A loss-framed message is thus recommended for message framing to promote vaccine uptake among millennials. These findings provide useful information in understanding the impact of message framing on behavioural intentions, especially in the context of vaccine uptake intentions of Millennials in South India.