BackgroundDuring the first year of the pandemic, essential workers faced higher rates of SARS-CoV-2 infection and COVID-19 mortality than non-essential workers. It is unknown whether disparities in pandemic-related mortality across occupational sectors have continued to occur, amidst SARS-CoV-2 variants and vaccine availability.MethodsWe obtained data on all deaths occurring in the state of California from 2016 through 2021. We restricted our analysis to California residents who were working age (18–65 years at time of death) and died of natural causes. Occupational sector was classified into 9 essential sectors; non-essential; or not in the labor market. We calculated the number of COVID-19 deaths in total and per capita that occurred in each occupational sector. Separately, using autoregressive integrated moving average models, we estimated total, per-capita, and relative excess natural-cause mortality by week between March 1, 2020, and November 30, 2021, stratifying by occupational sector. We additionally stratified analyses of occupational risk into regions with high versus low vaccine uptake, categorizing high-uptake regions as counties where at least 50% of the population completed a vaccination series by August 1, 2021.FindingsFrom March 2020 through November 2021, essential work was associated with higher COVID-19 and excess mortality compared with non-essential work, with the highest per-capita COVID-19 mortality in agriculture (131.8 per 100,000), transportation/logistics (107.1), manufacturing (103.3), and facilities (101.1). Essential workers continued to face higher COVID-19 and excess mortality during the period of widely available vaccines (March through November 2021). Between July and November 2021, emergency workers experienced higher per-capita COVID-19 mortality (113.7) than workers from any other sector. Essential workers faced the highest COVID-19 mortality in counties with low vaccination rates, a difference that was more pronounced during the period of the Delta surge in Summer 2021.InterpretationEssential workers have continued to bear the brunt of high COVID-19 and excess mortality throughout the pandemic, particularly in the agriculture, emergency, manufacturing, facilities, and transportation/logistics sectors. This high death toll has continued during periods of vaccine availability and the delta surge. In an ongoing pandemic without widespread vaccine coverage and anticipated threats of new variants, the US must actively adopt policies to more adequately protect essential workers.