Studies in high-income countries suggest that mortality is related to economic cycles, but few studies have examined how fluctuations in the economy influence mortality in low- and middle-income countries. We exploit regional variations in gross domestic product per capita (GDPpc) over the period 1980–2010 in Colombia to examine how changes in economic output relate to adult mortality. Data on the number of annual deaths at ages 20 years and older (n = 3,506,600) from mortality registries, disaggregated by age groups, sex and region, were linked to population counts for the period 1980–2010. We used region fixed effect models to examine whether changes in regional GDPpc were associated with changes in mortality. We carried out separate analyses for the periods 1980–1995 and 2000–2010 as well as by sex, distinguishing three age groups: 20–44 (predominantly young working adults), 45–64 (middle aged working adults), and 65+ (senior, predominantly retired individuals). The association between regional economic conditions and mortality varied by period and age groups. From 1980 to 1995, increases in GDPpc were unrelated to mortality at ages 20 to 64, but they were associated with reductions in mortality for senior men. In contrast, from 2000 to 2010, changes in GDPpc were not associated with old age mortality, while an increase in GDPpc was associated with a decline in mortality at ages 20–44 years. Analyses restricted to regions with high registration coverage yielded similar albeit less precise estimates for most sub-groups. The relationship between business cycles and mortality varied by period and age in Colombia. Most notably, mortality shifted from being acyclical to being countercyclical for males aged 20–44, while it shifted from being countercyclical to being acyclical for males aged 65+.