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Objectives While almost 60% of the world has received at least one dose of COVID-19 vaccine, the global distribution of vaccination has not been equitable. Only 4% of the population of low-income countries (LICs) has received a full primary vaccine series, compared with over 70% of the population of high-income nations.Design We used economic and epidemiological models, parameterised with public data on global vaccination and COVID-19 deaths, to estimate the potential benefits of scaling up vaccination programmes in LICs and lower-middle-income countries (LMICs) in 2022 in the context of global spread of the Omicron variant of SARS-CoV2.Setting Low-income and lower-middle-income nations.Main outcome measures Outcomes were expressed as number of avertable deaths through vaccination, costs of scale-up and cost per death averted. We conducted sensitivity analyses over a wide range of parameter estimates to account for uncertainty around key inputs.Findings Globally, universal vaccination in LIC/LMIC with three doses of an mRNA vaccine would result in an estimated 1.5 million COVID-19 deaths averted with a total estimated cost of US$61 billion and an estimated cost-per-COVID-19 death averted of US$40 800 (sensitivity analysis range: US$7400–US$81 500). Lower estimated infection fatality ratios, higher cost-per-dose and lower vaccine effectiveness or uptake lead to higher cost-per-death averted estimates in the analysis.Conclusions Scaling up COVID-19 global vaccination would avert millions of COVID-19 deaths and represents a reasonable investment in the context of the value of a statistical life. Given the magnitude of expected mortality facing LIC/LMIC without vaccination, this effort should be an urgent priority.