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In the 20th century, periods of macroeconomic growth have been associated with increases in population mortality. Factors that cause or mitigate this association are not well understood. Evidence suggests that social policy may buffer the deleterious impact of economic growth. We sought to explore associations between changing unemployment (as a proxy for economic change) and trends in mortality over 30 years in the context of varying social protection expenditures.We model change in all-cause mortality in 21 OECD (Organization for Economic Cooperation and Development) countries from 1980 to 2010. Data from the Comparative Welfare States Data Set and the WHO Mortality Database were used. A decrease in the unemployment rate was used as a proxy for economic growth and age-adjusted mortality rates as the outcome. Social protection expenditure was measured as percentage of gross domestic product expended.A 1% decrease in unemployment (i.e. the proxy for economic growth) was associated with a 0.24% increase in the overall mortality rate (95% confidence interval: 0.07;0.42) in countries with no changes in social protection. Reductions in social protection expenditure strengthened this association between unemployment and mortality. The magnitude of the association was diminished over time.Our results are consistent with the hypothesis that social protection policies that accompany economic growth can mitigate its potential deleterious effects on health. Further research should identify specific policies that are most effective.