OBJECTIVES To assess the comparative efficacy, immunogenicity and safety of COVID-19 vaccines on SARS CoV-2 of any type (wild-type or variant) as well as SARS CoV-2 variants of concern Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) in addition to any other newly discovered variants of concerns as identified by WHO. This is a protocol of a living systematic review and network meta-analysis of randomized controlled trials (RCTs) evaluating COVID-19 vaccines. The living systematic review is part of the larger COVID-NMA initiative, (27)which aims to provide decision-makers with a complete, high-quality and up-to-date living systematic review on interventions for preventing and treating COVID-19. (28) This protocol on SARS-COV2 vaccines is a sub-protocol within the COVID-NMA project. The NMA, where feasible, aims to provide results for all possible comparisons (direct and indirect) across different vaccines. This is the protocol for a Cochrane living systematic review. All results will be made available on the COVID-NMA platform (https://covid-nma.com) and updated weekly. As this is an emerging topic and knowledge about this infection is evolving rapidly, we will set up regular meetings with content experts to update the protocol (e.g., definition of the nodes of the network, effect modifiers) and specify other important aspects (e.g., margin of equivalence). The review is registered in Prospero CRD42021271897.