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ObjectiveTo assess the risk of death involving COVID-19 following infection from Omicron (B.1.1.539/BA.1) relative to Delta (B.1.617.2).DesignRetrospective cohort study.SettingEngland, UK, 1 December 2021 to 25 January 2022.Participants1,035,163 people aged 18-100 years who tested positive for SARS-CoV-2 in the national surveillance programme, and had an infection identified as either Omicron- or Delta compatible.Main outcome measuresDeath involving COVID-19 as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause-specific Cox proportional hazard regression models were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, Index of Multiple Deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Additionally, we tested for interactions between variant and sex, age, vaccination status and comorbidities.ResultsThe risk of death involving COVID-19 was 67% lower for Omicron compared to Delta and the reduction in the risk of death involving COVID-19 for Omicron compared to Delta was more pronounced in males than in females and in people under 70 years old than in people aged 70 years or over. Regardless of age, reduction of the risk of death from Omicron relative to Delta more was more pronounced in people who had received a booster than in those having received only two doses.ConclusionsOur results support early work showing the relative reduction in severity of Omicron compared to Delta in terms of hospitalisation and extends this research to assess COVID-19 mortality. Our work also highlights the importance of the vaccination booster campaign, where the reduction in risk of death involving COVID-19 is most pronounced in individuals who had received a booster.What is already known on this topicThe Omicron variant, which refers to the whole lineage (BA.1, BA.2, BA.3) had already been shown to be more transmissible than the Delta variant, but there is emerging evidence suggests that the risk of hospitalisation and risk of death within 28 days after a SARS-COV-2 test is lower. However, with a highly transmissible infection and high levels of population testing, definition of death within 28 days is more likely to be susceptible to misclassification bias due to asymptomatic or co-incidental infection. There is no study so far comparing the risk of COVID-19 death as identified from death certification records, with the cause of death assessed by the physician who attended the patient in the last illness.What this study addsUsing data from a large cohort of COVID-19 infections that occurred in December 2021, we examined the difference in the risk COVID-19 death, as identified from death certification records, between the Delta and Omicron BA.1 variant. Our study shows that risk of death involving COVID-19 was reduced by 67% following infection with the Omicron BA.1 variant relative to the Delta variant after adjusting for a wide range of potential confounders, including vaccination status and comorbidities. Importantly, we found that the relative risk of COVID-19 mortality following Omicron versus Delta infection varied by age and sex, with lower relative risk in younger individuals and for males than females. The reduction in risk of death involving COVID-19 was also most pronounced in individuals who had received a booster.