Objectives: In 2020, Croatia reported the first increase in the unemployment rate after six consecutive years of reduction in the number of unemployed persons. Unemployment is associated with an increase in morbidity and mortality among unemployed persons. We estimated the number of potential excess deaths that could be associated with an increase in unemployment seen after the beginning of the COVID-19 pandemic in 2020. ----- Study design: This was a cross-sectional analytic study. ----- Methods: We used previously published meta-analyzed hazard ratios for the unemployment-mortality association and unemployment and mortality data from the Croatian Bureau of Statistics to estimate 1-year age-standardized deaths potentially attributable to COVID-19-related unemployment for persons aged 20-64 in Croatia. ----- Results: In January 2021, we observed a 19% increase in unemployment among persons aged 20-64 years compared with February 2020 (prepandemic). This increase in unemployment could lead to 23 excess deaths among newly unemployed persons. This would constitute a 42% increase in the number of deaths and 29% of all deaths among this group. Deaths were disproportionately higher among men and those aged >40 years. ----- Conclusions: To mitigate the negative impact of COVID-19-related unemployment on population health, interventions that will reduce the further spread of SARS-CoV-2 and policies that will ensure economic recovery and reduction of unemployment are needed. Job skills training and provision of legal and welfare advice programs for unemployed persons should be integrated with health interventions.