Background and aimIncreased mortality during the COVID-19 pandemic is not explained exclusively by COVID-19 infection and its complications. We analysed non-COVID-19 causes of mortality in a population analysis based on data from the Spanish National Institute of Statistics.MethodsUsing monthly mortality data in Spain (January 2010–December 2020), we analysed deaths associated with cancer, blood, endocrine, mental, nervous, cardiovascular, respiratory and digestive diseases and explored the COVID-19 impact using a difference-in-difference strategy. We calculated monthly interannual variations in mortality and computed percentage change in terms of the log of deaths in monthhof yeartminus the log of deaths in monthhin the previous yeart−1.ResultsIn 2020 in Spain, mortality increased 17.9% compared with 2019. COVID-19 was the leading cause of death (n=60 358), followed by ischaemic heart disease (n=29 654). Throughout 2020, monthly interannual variations in cardiovascular mortality showed an average upward trend of 1.7%, while digestive, cancer and blood diseases showed a downward trend.ConclusionsDuring the COVID-19 pandemic in Spain in 2020, excess mortality was primarily related to cardiovascular mortality while mortality associated with digestive, cancer and blood diseases was reduced.